Ignite Creation Date:
2024-05-05 @ 12:08 PM
Last Modification Date:
2024-10-26 @ 9:21 AM
Study NCT ID:
NCT00256412
Status:
COMPLETED
Last Update Posted:
2008-06-05
First Post:
2005-11-16
Brief Title:
Essential Fatty Acids for Major Depression
Sponsor:
University of Iowa
Organization:
University of Iowa
Study Overview
Official Title:
Essential Fatty Acids in Management of MDD - A Pilot Study
Status:
COMPLETED
Status Verified Date:
2008-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a research study to determine whether omega-3 fatty acid supplementation when taken with the antidepressant medication escitalopram Lexapro helps to improve depressive symptoms in individuals who have major depressive disorder MDD
Omega-3 fatty acids are found in foods including walnuts some fruits and vegetables and coldwater fish such as herring mackerel sturgeon and anchovies
Omega-3 fatty acids are found in foods including walnuts some fruits and vegetables and coldwater fish such as herring mackerel sturgeon and anchovies
Detailed Description:
Primary aims
Aim 1 To determine whether measures of essential fatty acid EFA membrane composition predict symptom improvement during selective serotonin reuptake inhibitor SSRI treatment of major depressive disorder
Aim 2 To determine whether augmentation with the EFA eicosapentaenoic acid EPA is likely to benefit patients who have had an inadequate improvement following four weeks of SSRI monotherapy
Aim 3 To determine the degree to which improvement following omega-3 supplementation in SSRI partial responders reflects changes in the erythrocyte concentrations of EPA and DHA and in the ratio of EPA to arachidonic acid AA erythrocyte concentrations
Secondary Aim
To determine whether relationships between changes in tissue EFA concentrations and changes in depressive symptoms following omega-3 supplementation are mediated by changes in cytokine activity
Primary Hypotheses
Hypothesis 1 After four weeks of treatment with the SSRI escitalopram Montgomery-Asberg Depression Rating Scale MADRS scores will correlate positively with baseline RBC concentrations of EPA and DHA and negatively with baseline erythrocyte ratios of AA to EPA
Hypothesis 2 Among patients who continue to meet criteria for MDD after four weeks of treatment both those randomized to 7 grams and those randomized to 15 grams daily of EPA supplementation will show a greater mean improvement in MADRS scores after an additional six weeks than will those assigned to placebo supplementation
Hypothesis 3 After patients who have had inadequate antidepressant responses to SSRI treatment complete six weeks of augmentation with placebo or with 7 grams or 15 grams per day of EPA a relationships will exist between final MADRS scores and both the final RBC concentrations of DHA and EPA and the final RBC ratio of AA to EPA These relationships will resemble those between baseline RBC concentrations and subsequent responses to escitalopram and will suggest therapeutic ranges for these concentrations
Secondary Hypothesis
Among patients with erythrocyte EPA concentrations less than 082 at the beginning of the augmentation trial the association between subsequent changes in depressive symptoms and EPA tissue concentrations will be markedly reduced by the introduction of changes in IL-1 beta IL-10 and PGE2 into the model
Study Design
Phase one is a four-week open trial and is designed to test specific response predictors A subset of subjects who complete phase one will enter phase two a six-week double-blind placebo-controlled trial designed to show whether eicosapentaenoic acid EPA is an effective augmentation agent in patients who have had an inadequate antidepressant response
A pilot of thirty 30 subjects aged 18-55 years with current major depressive disorder who have taken not regularly taken antidepressants in the previous month Cognitively impaired subjects will not be included
This is a pilot study designed to demonstrate the feasibility for an NIMH application It is not currently powered to statistically test the listed hypotheses
Study outcomesendpoints
The primary outcomes for both phases will be the final MADRS score
Study Procedures
Subjects will be recruited through advertisement and through the University of Iowa Hospitals and Clinics UIHC adult clinic Advertisements will also be placed in the newspapers of cities within a 100-mile radius of UIHC
Screening procedures
The studys research associate will screen calls contact respondents and administer the screening to determine eligibility Those who appear to satisfy entry criteria will be given appointments to meet with the PI and Co-PI If the in-person evaluation confirms the subjects eligibility he or she will be given a consent form and be invited to ask any remaining questions he or she might have The protocol could begin at that visit
Study Intervention
Active study agents Escitalopram and eicosupentaenoic acid EPA A variety of antidepressants are available for the treatment of Major Depressive Disorder MDD A number of psychotherapeutic approaches also have demonstrated effectiveness Potential subjects could receive both escitalopram and EPA without participating in the study
Placebo study agents Placebo capsules will match the EPA capsules
Storage
Drug will be locked and maintained in the medical education building Data forms and computerized data will be stored in the University of Iowa Medical Education Building Offices and cabinets will be locked computer files will be password protected The lab of Arthur Spector MD will analyze the blood samples
Administration
In phase one subject will be given a 4 week supply of 10 mg escitalopram Lexapro and instructed to take one pill a day for 4 weeks
If eligible for phase 2 of the study subject will continue to take 10 mg of escitalopram but will also be randomly assigned to take in addition either 07 grams or 15grams of the EPA or a placebo
If depression symptoms have improved by greater than 50 at the end of week 4 subject will be given a 1 month supply of escitalopram and will be assisted in obtaining psychiatric care in their area
If depression symptoms have not improved by greater than 50 at the end of week 4 subject will be invited to participate in Phase 2 of the study
The protocol will begin with the administration of a structured diagnostic interview the Structured Clinical Interview for DSM IV Diagnosis SCID and two depression rating scales the Montgomery Asburg Depression Rating Scale MADRS and the Hamilton Rating Scale HRS Two tubes of blood will be drawn one for erythrocyte EFA concentration determination and the other for quantification of inflammatory markers c-reactive protein Subjects will then be supplied with a one-month supply of escitalopram Lexapro with instructions to take one 10mg capsule each morning Return visits at two weeks and four weeks will be scheduled and subjects will be instructed to return with any remaining medication
Subjects will be contacted at weekly intervals During a brief telephone conversation he or she will ask whether the subject has any questions or has experienced any troublesome side effects
Those who meet the criteria for inadequate escitalopram response described above will be invited to participate in a six-week trial of supplemental omega-3 Subjects will continue taking escitalopram at the previous dose of 10mg daily but will be randomly assigned to take in addition either 07 grams or 15 grams of the eicosapentaenoic acid EPA or a placebo
Visits for phase 2 will be scheduled at weeks 6 8 and 10 At week 4 and 10 blood samples for erythrocyte EFA concentrations and cytokine determinations will be drawn MADRS will be rated on these visits
Aim 1 To determine whether measures of essential fatty acid EFA membrane composition predict symptom improvement during selective serotonin reuptake inhibitor SSRI treatment of major depressive disorder
Aim 2 To determine whether augmentation with the EFA eicosapentaenoic acid EPA is likely to benefit patients who have had an inadequate improvement following four weeks of SSRI monotherapy
Aim 3 To determine the degree to which improvement following omega-3 supplementation in SSRI partial responders reflects changes in the erythrocyte concentrations of EPA and DHA and in the ratio of EPA to arachidonic acid AA erythrocyte concentrations
Secondary Aim
To determine whether relationships between changes in tissue EFA concentrations and changes in depressive symptoms following omega-3 supplementation are mediated by changes in cytokine activity
Primary Hypotheses
Hypothesis 1 After four weeks of treatment with the SSRI escitalopram Montgomery-Asberg Depression Rating Scale MADRS scores will correlate positively with baseline RBC concentrations of EPA and DHA and negatively with baseline erythrocyte ratios of AA to EPA
Hypothesis 2 Among patients who continue to meet criteria for MDD after four weeks of treatment both those randomized to 7 grams and those randomized to 15 grams daily of EPA supplementation will show a greater mean improvement in MADRS scores after an additional six weeks than will those assigned to placebo supplementation
Hypothesis 3 After patients who have had inadequate antidepressant responses to SSRI treatment complete six weeks of augmentation with placebo or with 7 grams or 15 grams per day of EPA a relationships will exist between final MADRS scores and both the final RBC concentrations of DHA and EPA and the final RBC ratio of AA to EPA These relationships will resemble those between baseline RBC concentrations and subsequent responses to escitalopram and will suggest therapeutic ranges for these concentrations
Secondary Hypothesis
Among patients with erythrocyte EPA concentrations less than 082 at the beginning of the augmentation trial the association between subsequent changes in depressive symptoms and EPA tissue concentrations will be markedly reduced by the introduction of changes in IL-1 beta IL-10 and PGE2 into the model
Study Design
Phase one is a four-week open trial and is designed to test specific response predictors A subset of subjects who complete phase one will enter phase two a six-week double-blind placebo-controlled trial designed to show whether eicosapentaenoic acid EPA is an effective augmentation agent in patients who have had an inadequate antidepressant response
A pilot of thirty 30 subjects aged 18-55 years with current major depressive disorder who have taken not regularly taken antidepressants in the previous month Cognitively impaired subjects will not be included
This is a pilot study designed to demonstrate the feasibility for an NIMH application It is not currently powered to statistically test the listed hypotheses
Study outcomesendpoints
The primary outcomes for both phases will be the final MADRS score
Study Procedures
Subjects will be recruited through advertisement and through the University of Iowa Hospitals and Clinics UIHC adult clinic Advertisements will also be placed in the newspapers of cities within a 100-mile radius of UIHC
Screening procedures
The studys research associate will screen calls contact respondents and administer the screening to determine eligibility Those who appear to satisfy entry criteria will be given appointments to meet with the PI and Co-PI If the in-person evaluation confirms the subjects eligibility he or she will be given a consent form and be invited to ask any remaining questions he or she might have The protocol could begin at that visit
Study Intervention
Active study agents Escitalopram and eicosupentaenoic acid EPA A variety of antidepressants are available for the treatment of Major Depressive Disorder MDD A number of psychotherapeutic approaches also have demonstrated effectiveness Potential subjects could receive both escitalopram and EPA without participating in the study
Placebo study agents Placebo capsules will match the EPA capsules
Storage
Drug will be locked and maintained in the medical education building Data forms and computerized data will be stored in the University of Iowa Medical Education Building Offices and cabinets will be locked computer files will be password protected The lab of Arthur Spector MD will analyze the blood samples
Administration
In phase one subject will be given a 4 week supply of 10 mg escitalopram Lexapro and instructed to take one pill a day for 4 weeks
If eligible for phase 2 of the study subject will continue to take 10 mg of escitalopram but will also be randomly assigned to take in addition either 07 grams or 15grams of the EPA or a placebo
If depression symptoms have improved by greater than 50 at the end of week 4 subject will be given a 1 month supply of escitalopram and will be assisted in obtaining psychiatric care in their area
If depression symptoms have not improved by greater than 50 at the end of week 4 subject will be invited to participate in Phase 2 of the study
The protocol will begin with the administration of a structured diagnostic interview the Structured Clinical Interview for DSM IV Diagnosis SCID and two depression rating scales the Montgomery Asburg Depression Rating Scale MADRS and the Hamilton Rating Scale HRS Two tubes of blood will be drawn one for erythrocyte EFA concentration determination and the other for quantification of inflammatory markers c-reactive protein Subjects will then be supplied with a one-month supply of escitalopram Lexapro with instructions to take one 10mg capsule each morning Return visits at two weeks and four weeks will be scheduled and subjects will be instructed to return with any remaining medication
Subjects will be contacted at weekly intervals During a brief telephone conversation he or she will ask whether the subject has any questions or has experienced any troublesome side effects
Those who meet the criteria for inadequate escitalopram response described above will be invited to participate in a six-week trial of supplemental omega-3 Subjects will continue taking escitalopram at the previous dose of 10mg daily but will be randomly assigned to take in addition either 07 grams or 15 grams of the eicosapentaenoic acid EPA or a placebo
Visits for phase 2 will be scheduled at weeks 6 8 and 10 At week 4 and 10 blood samples for erythrocyte EFA concentrations and cytokine determinations will be drawn MADRS will be rated on these visits
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