Ignite Creation Date:
2024-10-26 @ 3:39 PM
Last Modification Date:
2024-10-26 @ 3:39 PM
Study NCT ID:
NCT06579391
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-03-31
Brief Title:
Targeted Nutritional Supplement After Lumbar Spine Surgery A Randomized Placebo-Controlled Double-Blind Trial
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Effects of a Targeted Nutritional Supplement on Muscle Volume and Function After Posterior Lumbar Spine Surgery A Randomized Placebo-Controlled Double-Blind Clinical Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The goal of this clinical trial is to prospectively evaluate the effects of essential amino acid EAA supplementation on the volume and structure of the muscles surrounding the spine paraspinal musculature The main questions it aims to answer are
Does EAA supplementation preserve paraspinal muscle volume PMV and influence changes to spinal alignment following lumbar spine surgery
Does preserving paraspinal muscle volume PMV improve post-operative functional status
Does preserving PMV reduce post-operative complications pain and opioid consumption
Participants will be asked to
Consume either EAA supplement or placebo alanine twice daily for one week before and two weeks after lumbar spine surgery
Record pain levels and medication use in a diary
Perform functional assessments at routine follow-up visits after surgery
Undergo blood draws to monitor nutrition status and health
Undergo one spine magnetic resonance imaging MRI before surgery as part of routine surgical planning
Undergo one additional spine MRI after surgery to monitor PMV after treatment
Researchers will compare the group that consumed EAA supplement and the group that consumed placebo to see if there is a difference in paraspinal muscle volume changes and measures of spinal alignment functional abilities pain levels and opioid use
Does EAA supplementation preserve paraspinal muscle volume PMV and influence changes to spinal alignment following lumbar spine surgery
Does preserving paraspinal muscle volume PMV improve post-operative functional status
Does preserving PMV reduce post-operative complications pain and opioid consumption
Participants will be asked to
Consume either EAA supplement or placebo alanine twice daily for one week before and two weeks after lumbar spine surgery
Record pain levels and medication use in a diary
Perform functional assessments at routine follow-up visits after surgery
Undergo blood draws to monitor nutrition status and health
Undergo one spine magnetic resonance imaging MRI before surgery as part of routine surgical planning
Undergo one additional spine MRI after surgery to monitor PMV after treatment
Researchers will compare the group that consumed EAA supplement and the group that consumed placebo to see if there is a difference in paraspinal muscle volume changes and measures of spinal alignment functional abilities pain levels and opioid use
Detailed Description:
This study is a randomized placebo-controlled double-blinded single-center clinical trial to elucidate the effects of perioperative essential amino acid nutritional supplementation in pursuit of the following aim and covariates
Specific Aim 1 Preserve paraspinal muscle volume and assess impact on spine sagittal balance through measurement of radiographic parameters Paraspinal muscle atrophy following lumbar spine surgery has been correlated with worse clinical outcomes It is still not understood whether iatrogenic denervation immobilization or nutritional deficiencies lead to the reduced volume in the paraspinal muscles Investigators will utilize pre- and post-operative MRI scans to quantify changes in paraspinal and psoas muscle cross-sectional area and fatty infiltration and measure sagittal vertical axis pelvic incidence lumbar lordosis and pelvic tilt as muscle quality has been correlated with spine balance and degeneration as well as bone quality
Specific Aim 2 Assess clinical outcomes postoperatively to determine any possible effect of paraspinal muscle volumes on variability in functional status Functional assessments will be made using established validated clinical outcomes measures at baseline and up to 2 years postoperatively Postoperative adverse events will be recorded throughout the duration of the study as well as markers of nutritional status using a validated dietary questionnaire and blood sampling Results will be compared between treatment and control groups to determine if functional status is associated with variability in outcomes related to preservation of native paraspinal muscle volume postoperatively
Specific Aim 3 Evaluate postoperative pain and opioid consumption postoperatively to determine any possible effect of pain on variability in paraspinal muscle volumes Patient-reported pain and opioid consumption will be evaluated perioperatively with a daily pain diary clinician-administered pain assessments and review of the state-controlled substances database CURES Pain ratings mean morphine equivalents time to baseline preoperative opioid consumption and time to opioid discontinuation will be compared between treatment and control groups to determine any relationship between postoperative pain levels on variability in outcomes related to preservation of native paraspinal muscle volume following surgery
Description of Procedures
Study team members will review the patient medical record for the minimal amount of health information necessary to determine eligibility in the study prior to obtaining informed consent Patients undergoing lumbar spine surgery that meet eligibility requirements-determined using standard nutritional and lumbar surgical clinical research inclusionexclusion criteria applied according to the judgment of the investigator-will receive standardized written and verbal information about the trial from the investigators listed in the study team For non-English speaking participants an interpreter will be involved in the consenting process
A member of the research team will be unblinded and responsible for block randomization of participants with 11 allocation to EAA and placebo groups N44 each group using Excel 2016 Microsoft The University of California Irvine UCI Investigational Drug Services Pharmacy IDS Pharmacy is responsible for receiving labeling storing and distributing the products and will collect product containersany unused products at the conclusion of the supplement period as outlined in the study protocol The remainder of the study team including the primary investigator and co-researchers and the statistician responsible for data analysis will be blinded to randomization
Demographic and baseline information regarding nutritional functional and frailty status will be collected at the baseline visit within 6 weeks to 1 week prior to surgery including ambulatory status independent cane walker wheelchair food preferences omnivorous pescatarian vegan vegetarian Protein Screener 55 a validated questionnaire to screen for low dietary protein intake in the elderly modified Fragility Index a validated risk stratification tool in lumbar spine surgery and baseline labs including serum albumin prealbumin and transferrin as markers of nutritional status and inflammation functionality pain scores and medication use From 1 week prior to surgery until 2 weeks postoperatively patients will consume either a commercially available EAA supplement-containing L-leucine 36g L-lysine as L-lysine HCl 32g L-phenylalanine 32g L-valine 24g L-threonine 28g L-isoleucine 20g L-methionine 06g and L-histidine as L-histidine HCl 22g Joint Replacement Mend Labs New York NY twice daily-or calorically-equivalent placebo alanine 20g twice daily
Fellowship-trained spine surgeons will perform all lumbar decompression andor fusion surgeries using the same posterior operative approach and instrumented fusion of unstable segments if clinically indicated All patients are hospitalized from the day of surgery until discharge with the total length of stay dependent on postoperative pain control and progress in physical therapy Patient-reported pain will be evaluated with a daily pain diary using the Numerical Pain Rating Scale beginning 1 week prior to surgery for at least 2 weeks postoperatively or until termination of opioid consumption for a maximum of 1 month Patients will be educated to also record pain levels each time they take an opioid Opioid consumption-including oxycodone hydrocodone morphine codeine fentanyl hydromorphone and tramadol-will be captured simultaneously through a pain medication diary and compared between treatment groups as mean morphine equivalents Time to less than baseline opioid consumption and time to opioid discontinuation will also be compared between treatment groups Clinician-administered patient pain ratings using the Visual Analogue Score will be recorded at baseline on the day of surgery and at each postoperative visit
Timeline of Study Procedures
1 Screening visit within 6 months to 6 weeks prior to surgery date consent physical exam pregnancy test if appropriate review of lumbar MRI approximately 1 hour
2 Preoperative visit within 6 weeks to 1 week prior to surgery physical exam baseline labs baseline functional mobility and pain assessment CURES database review patient education on self-reporting pain opioid consumption consumption of other medications and EAA supplementation or placebo consumption approximately 2 hours EAA and placebo will be provided by the manufacturer in the same containers with the same scoop size and the same label instructing patients consume one serving twice a day beginning one before their surgery and for 2 weeks after These instructions and labels will be provided by Mend and they align with previously studied protocols where the supplement has been fond to be safe Investigators hope in using the product as directed by Mend to reduce risk for participants and decrease confusion as they can follow the package information
3 Surgery day all patients are hospitalized from the day of surgery until discharge with the total length of stay dependent on postoperative pain control and physical therapy progress Patients will receive this surgery and the associated postoperative inpatient stay as part of standard of care regardless of their involvement in this study Research related data collection aside from standard of care during their perioperative inpatient stay will be approximately 1 hour approximately 1 hour
4 Postoperative follow-up at 2 weeks - 5 days physical exam functional mobility and pain assessment labs review of patient-reported daily pain levels review of CURES and opioidmedication consumption review of patient-reported EAA supplementation or placebo consumption logs approximately 1 hour
5 Postoperative follow-up at 6-8 weeks - 5 days physical exam functional mobility and pain assessment labs review of CURES and opioidmedication consumption approximately 30 minutes
6 Postoperative lumbar MRI without contrast obtained at 8-10 weeks 1 hour
7 Postoperative follow-up at 12 weeks - 5 days physical exam review MRI results functional mobility and pain assessment review of CURES and opioidmedication consumption approximately 1 hour
Statistical Plan
Power analysis Sample size analysis was performed a priori using data from the literature evaluating muscle atrophy with and without nutritional supplementation in patients with total knee arthroplasty as there is no data assessing paraspinal muscle volume after lumbar spine surgery with an expected difference in primary outcome measure of 49 134 - 19 in control and 85 in experimental Using two independent groups a continuous variable primary endpoint an assumed 2-tailed type-1 error rate of 005 and a power value of 80 we require a minimum total of 88 patients with 44 in each group
Overall Baseline characteristics will be compared between the groups using independent t tests or the Wilcoxon rank sum test if the characteristics were not normally distributed for continuous measures and the chi-square test for categorical measures Continuous variables will be described using the mean and standard deviation Categorical variables will be described using absolute frequencies Pearsons correlation coefficient r will be used to assess relationships between paraspinal muscle CSA opioid consumption as morphine milligram equivalents MME clinical functional outcome measures and postoperative complications A two-way repeated measured analysis of variance ANOVA will evaluate chronological changes in continuous variables between the two groups Significance will be set at p 005
Specific Aim 1 Axial T2-weighted lumbar spine MRI at the levels of the L1-5 intervertebral discs using a 3 Tesla 3T MRI with a phased-array surface coil will be completed within 6 months to 6 weeks about 1 and a half months prior to surgery and prior to treatment intervention and will be compared to the repeat MRI completed at 8-10 weeks postoperatively Bilateral paraspinal muscle cross-sectional area CSA will be measured by two experienced musculoskeletal radiologists marking the borders of these muscles Proton density fat fraction will be used to quantify the proportion of fatty infiltration and overall atrophy will be qualitatively rated based on visual assessment using a visual scale modified from the Goutallier grading system Sagittal spinopelvic alignment parameters including sagittal vertical axis pelvic incidence lumbar lordosis and pelvic tilt will be measured on both the pre and postoperative MRIs The intraclass correlation coefficient for this measurement will be evaluated and interpreted according to the predetermined guidelines
Specific Aim 2 Functional status will be assessed for each treatment arm at baseline 2 weeks 6 weeks and 3 months postoperatively using established validated clinical outcome measures completed with a trained member of research staff the Oswestry Disability Index 21A 36-Item Short Form Health Survey SF-36 Patient-Reported Outcomes Measurement Information System PROMIS Physical Function EuroQol-5 Dimension 5 Levels EQ-5D-5L 6-minute walk test and 5 repetitive sit to stand test Preoperative mortality and morbidity risk will be controlled between treatment groups using the modified Frailty Index Postoperative adverse events will be recorded throughout the duration of the study including but not limited to hospital length of stay surgical site infections unplanned reoperation mortality and medical complications requiring intervention
Specific Aim 3 Patient-reported pain will be evaluated with a daily pain diary using the Numerical Pain Rating Scale beginning 1 week prior to surgery for at least 2 weeks postoperatively or until termination of opioid consumption for a maximum of 1 month Patients will be educated to also record pain levels each time they Opioid consumption-including oxycodone hydrocodone morphine codeine fentanyl hydromorphone and tramadol-will be captured simultaneously through a pain medication diary and compared between treatment groups as MME
Safety Monitoring
A Data Safety Monitoring Board DSMB consisting of 7 UCI faculty members from various relevant disciplines-including orthopaedic surgery anesthesiology nutrition pharmacology biostatistics-has been assembled to ensure the safety of all study participants throughout the duration of the study period At the first safety meeting prior to subject enrollment the DSMB will discuss the protocol and agree upon guidelines to study monitoring Subsequently study data will be evaluated continuously by the study team and meetings of the DSMB will be held at least two times a year every 6 months As part of the purpose of the study is to evaluate the impact of amino acid supplementation on functionalclinical outcomes pain and opioid use data ensuring compliance in supplement ingestion pain levels medication use functional outcomes and adverse events will be continuously documented No adverse outcomes are expected given that the amino acid supplement is commercially available and has shown to be safe for human consumption However unscheduled emergency meetings may be called at any time by the DSMB or the study investigators should participant safety questions or other unanticipated problems or adverse events arise-such as renal failure severe GI distress or melena Safety updates and reports will be submitted to the UCI Institutional Review Board with the continuing application each year
Specific Aim 1 Preserve paraspinal muscle volume and assess impact on spine sagittal balance through measurement of radiographic parameters Paraspinal muscle atrophy following lumbar spine surgery has been correlated with worse clinical outcomes It is still not understood whether iatrogenic denervation immobilization or nutritional deficiencies lead to the reduced volume in the paraspinal muscles Investigators will utilize pre- and post-operative MRI scans to quantify changes in paraspinal and psoas muscle cross-sectional area and fatty infiltration and measure sagittal vertical axis pelvic incidence lumbar lordosis and pelvic tilt as muscle quality has been correlated with spine balance and degeneration as well as bone quality
Specific Aim 2 Assess clinical outcomes postoperatively to determine any possible effect of paraspinal muscle volumes on variability in functional status Functional assessments will be made using established validated clinical outcomes measures at baseline and up to 2 years postoperatively Postoperative adverse events will be recorded throughout the duration of the study as well as markers of nutritional status using a validated dietary questionnaire and blood sampling Results will be compared between treatment and control groups to determine if functional status is associated with variability in outcomes related to preservation of native paraspinal muscle volume postoperatively
Specific Aim 3 Evaluate postoperative pain and opioid consumption postoperatively to determine any possible effect of pain on variability in paraspinal muscle volumes Patient-reported pain and opioid consumption will be evaluated perioperatively with a daily pain diary clinician-administered pain assessments and review of the state-controlled substances database CURES Pain ratings mean morphine equivalents time to baseline preoperative opioid consumption and time to opioid discontinuation will be compared between treatment and control groups to determine any relationship between postoperative pain levels on variability in outcomes related to preservation of native paraspinal muscle volume following surgery
Description of Procedures
Study team members will review the patient medical record for the minimal amount of health information necessary to determine eligibility in the study prior to obtaining informed consent Patients undergoing lumbar spine surgery that meet eligibility requirements-determined using standard nutritional and lumbar surgical clinical research inclusionexclusion criteria applied according to the judgment of the investigator-will receive standardized written and verbal information about the trial from the investigators listed in the study team For non-English speaking participants an interpreter will be involved in the consenting process
A member of the research team will be unblinded and responsible for block randomization of participants with 11 allocation to EAA and placebo groups N44 each group using Excel 2016 Microsoft The University of California Irvine UCI Investigational Drug Services Pharmacy IDS Pharmacy is responsible for receiving labeling storing and distributing the products and will collect product containersany unused products at the conclusion of the supplement period as outlined in the study protocol The remainder of the study team including the primary investigator and co-researchers and the statistician responsible for data analysis will be blinded to randomization
Demographic and baseline information regarding nutritional functional and frailty status will be collected at the baseline visit within 6 weeks to 1 week prior to surgery including ambulatory status independent cane walker wheelchair food preferences omnivorous pescatarian vegan vegetarian Protein Screener 55 a validated questionnaire to screen for low dietary protein intake in the elderly modified Fragility Index a validated risk stratification tool in lumbar spine surgery and baseline labs including serum albumin prealbumin and transferrin as markers of nutritional status and inflammation functionality pain scores and medication use From 1 week prior to surgery until 2 weeks postoperatively patients will consume either a commercially available EAA supplement-containing L-leucine 36g L-lysine as L-lysine HCl 32g L-phenylalanine 32g L-valine 24g L-threonine 28g L-isoleucine 20g L-methionine 06g and L-histidine as L-histidine HCl 22g Joint Replacement Mend Labs New York NY twice daily-or calorically-equivalent placebo alanine 20g twice daily
Fellowship-trained spine surgeons will perform all lumbar decompression andor fusion surgeries using the same posterior operative approach and instrumented fusion of unstable segments if clinically indicated All patients are hospitalized from the day of surgery until discharge with the total length of stay dependent on postoperative pain control and progress in physical therapy Patient-reported pain will be evaluated with a daily pain diary using the Numerical Pain Rating Scale beginning 1 week prior to surgery for at least 2 weeks postoperatively or until termination of opioid consumption for a maximum of 1 month Patients will be educated to also record pain levels each time they take an opioid Opioid consumption-including oxycodone hydrocodone morphine codeine fentanyl hydromorphone and tramadol-will be captured simultaneously through a pain medication diary and compared between treatment groups as mean morphine equivalents Time to less than baseline opioid consumption and time to opioid discontinuation will also be compared between treatment groups Clinician-administered patient pain ratings using the Visual Analogue Score will be recorded at baseline on the day of surgery and at each postoperative visit
Timeline of Study Procedures
1 Screening visit within 6 months to 6 weeks prior to surgery date consent physical exam pregnancy test if appropriate review of lumbar MRI approximately 1 hour
2 Preoperative visit within 6 weeks to 1 week prior to surgery physical exam baseline labs baseline functional mobility and pain assessment CURES database review patient education on self-reporting pain opioid consumption consumption of other medications and EAA supplementation or placebo consumption approximately 2 hours EAA and placebo will be provided by the manufacturer in the same containers with the same scoop size and the same label instructing patients consume one serving twice a day beginning one before their surgery and for 2 weeks after These instructions and labels will be provided by Mend and they align with previously studied protocols where the supplement has been fond to be safe Investigators hope in using the product as directed by Mend to reduce risk for participants and decrease confusion as they can follow the package information
3 Surgery day all patients are hospitalized from the day of surgery until discharge with the total length of stay dependent on postoperative pain control and physical therapy progress Patients will receive this surgery and the associated postoperative inpatient stay as part of standard of care regardless of their involvement in this study Research related data collection aside from standard of care during their perioperative inpatient stay will be approximately 1 hour approximately 1 hour
4 Postoperative follow-up at 2 weeks - 5 days physical exam functional mobility and pain assessment labs review of patient-reported daily pain levels review of CURES and opioidmedication consumption review of patient-reported EAA supplementation or placebo consumption logs approximately 1 hour
5 Postoperative follow-up at 6-8 weeks - 5 days physical exam functional mobility and pain assessment labs review of CURES and opioidmedication consumption approximately 30 minutes
6 Postoperative lumbar MRI without contrast obtained at 8-10 weeks 1 hour
7 Postoperative follow-up at 12 weeks - 5 days physical exam review MRI results functional mobility and pain assessment review of CURES and opioidmedication consumption approximately 1 hour
Statistical Plan
Power analysis Sample size analysis was performed a priori using data from the literature evaluating muscle atrophy with and without nutritional supplementation in patients with total knee arthroplasty as there is no data assessing paraspinal muscle volume after lumbar spine surgery with an expected difference in primary outcome measure of 49 134 - 19 in control and 85 in experimental Using two independent groups a continuous variable primary endpoint an assumed 2-tailed type-1 error rate of 005 and a power value of 80 we require a minimum total of 88 patients with 44 in each group
Overall Baseline characteristics will be compared between the groups using independent t tests or the Wilcoxon rank sum test if the characteristics were not normally distributed for continuous measures and the chi-square test for categorical measures Continuous variables will be described using the mean and standard deviation Categorical variables will be described using absolute frequencies Pearsons correlation coefficient r will be used to assess relationships between paraspinal muscle CSA opioid consumption as morphine milligram equivalents MME clinical functional outcome measures and postoperative complications A two-way repeated measured analysis of variance ANOVA will evaluate chronological changes in continuous variables between the two groups Significance will be set at p 005
Specific Aim 1 Axial T2-weighted lumbar spine MRI at the levels of the L1-5 intervertebral discs using a 3 Tesla 3T MRI with a phased-array surface coil will be completed within 6 months to 6 weeks about 1 and a half months prior to surgery and prior to treatment intervention and will be compared to the repeat MRI completed at 8-10 weeks postoperatively Bilateral paraspinal muscle cross-sectional area CSA will be measured by two experienced musculoskeletal radiologists marking the borders of these muscles Proton density fat fraction will be used to quantify the proportion of fatty infiltration and overall atrophy will be qualitatively rated based on visual assessment using a visual scale modified from the Goutallier grading system Sagittal spinopelvic alignment parameters including sagittal vertical axis pelvic incidence lumbar lordosis and pelvic tilt will be measured on both the pre and postoperative MRIs The intraclass correlation coefficient for this measurement will be evaluated and interpreted according to the predetermined guidelines
Specific Aim 2 Functional status will be assessed for each treatment arm at baseline 2 weeks 6 weeks and 3 months postoperatively using established validated clinical outcome measures completed with a trained member of research staff the Oswestry Disability Index 21A 36-Item Short Form Health Survey SF-36 Patient-Reported Outcomes Measurement Information System PROMIS Physical Function EuroQol-5 Dimension 5 Levels EQ-5D-5L 6-minute walk test and 5 repetitive sit to stand test Preoperative mortality and morbidity risk will be controlled between treatment groups using the modified Frailty Index Postoperative adverse events will be recorded throughout the duration of the study including but not limited to hospital length of stay surgical site infections unplanned reoperation mortality and medical complications requiring intervention
Specific Aim 3 Patient-reported pain will be evaluated with a daily pain diary using the Numerical Pain Rating Scale beginning 1 week prior to surgery for at least 2 weeks postoperatively or until termination of opioid consumption for a maximum of 1 month Patients will be educated to also record pain levels each time they Opioid consumption-including oxycodone hydrocodone morphine codeine fentanyl hydromorphone and tramadol-will be captured simultaneously through a pain medication diary and compared between treatment groups as MME
Safety Monitoring
A Data Safety Monitoring Board DSMB consisting of 7 UCI faculty members from various relevant disciplines-including orthopaedic surgery anesthesiology nutrition pharmacology biostatistics-has been assembled to ensure the safety of all study participants throughout the duration of the study period At the first safety meeting prior to subject enrollment the DSMB will discuss the protocol and agree upon guidelines to study monitoring Subsequently study data will be evaluated continuously by the study team and meetings of the DSMB will be held at least two times a year every 6 months As part of the purpose of the study is to evaluate the impact of amino acid supplementation on functionalclinical outcomes pain and opioid use data ensuring compliance in supplement ingestion pain levels medication use functional outcomes and adverse events will be continuously documented No adverse outcomes are expected given that the amino acid supplement is commercially available and has shown to be safe for human consumption However unscheduled emergency meetings may be called at any time by the DSMB or the study investigators should participant safety questions or other unanticipated problems or adverse events arise-such as renal failure severe GI distress or melena Safety updates and reports will be submitted to the UCI Institutional Review Board with the continuing application each year
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None