Ignite Creation Date:
2024-06-16 @ 11:50 AM
Last Modification Date:
2024-10-26 @ 3:31 PM
Study NCT ID:
NCT06446908
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-06-06
First Post:
2024-05-27
Brief Title:
Acceptability and Feasibility of a New Approach to Engage Patients With Steatotic Liver Disease in Physical Activity
Sponsor:
Hopital Montfort
Organization:
Hopital Montfort
Study Overview
Official Title:
Acceptability and Feasibility of a New Approach to Engage Patients With Steatotic Liver Disease in Physical Activity
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-05
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:
Steatosis is the building of fat in the liver Steatotic liver disease SLD regroups MASLD metabolic dysfunction-associated steatotic liver disease and MASH metabolic dysfunction-associated steatohepatitis ie MASLD with inflammation An estimated 30 of the population worldwide has MASLD and 5 of Canadians have MASH MASH is a leading cause of liver transplantation in Canada There is no cure for SLD and the treatment relies on diet weight loss and physical activity PA
Is a counselling intervention to help patients progressively engage in more PA a feasible and acceptable approach Objectives This proposal has three primary objectives 1 To assess the feasibility of our PA counselling intervention to be delivered online with SLD patients 2 To evaluate the acceptability of our intervention 3 To evaluate the feasibility of the study methodsprocedures
Methodology This study is an open-label mono-centred single-case experimental design with multiple base levels The study will comprise 3 phases alternating periods of observation A and 1 period of counselling B with an A1-B-A2 design
PA will be assessed continuously using an accelerometer for 7 to 14 days per A phase During phase B participants will receive the intervention ie 6 x 45-minute real-time face-to-face virtual sessions with a PA counsellor
Based on past studies our sample size will be 12 participants They will be recruited through the hepatology clinic at Hôpital Montfort
The primary outcomes of the project are to evaluate the feasibility and acceptability of the trial and intervention The secondary outcomes are Daily PA time and biologicalimaging data evolution
Is a counselling intervention to help patients progressively engage in more PA a feasible and acceptable approach Objectives This proposal has three primary objectives 1 To assess the feasibility of our PA counselling intervention to be delivered online with SLD patients 2 To evaluate the acceptability of our intervention 3 To evaluate the feasibility of the study methodsprocedures
Methodology This study is an open-label mono-centred single-case experimental design with multiple base levels The study will comprise 3 phases alternating periods of observation A and 1 period of counselling B with an A1-B-A2 design
PA will be assessed continuously using an accelerometer for 7 to 14 days per A phase During phase B participants will receive the intervention ie 6 x 45-minute real-time face-to-face virtual sessions with a PA counsellor
Based on past studies our sample size will be 12 participants They will be recruited through the hepatology clinic at Hôpital Montfort
The primary outcomes of the project are to evaluate the feasibility and acceptability of the trial and intervention The secondary outcomes are Daily PA time and biologicalimaging data evolution
Detailed Description:
Background and rationale This pilot trial aims to evaluate the feasibility and acceptability of a counselling intervention on physical activity in patients with liver steatosis primary aim and changes in molecular outcomes exploratory aim
Liver steatosis is the build-up of fat in the form of lipid droplets inside hepatocytes liver cells Although it is a form of energy storage it is considered pathological when more than 5 of hepatocytes demonstrate fat infiltration on a liver biopsy or imaging ultrasound magnetic resonance or computed tomography Until recently liver steatosis was described as two entities with a clinicopathological continuum non-alcoholic fatty liver disease NAFLD and non-alcoholic steatohepatitis NASH ie NAFLD with inflammation NAFLDNASH is strongly associated with features of the metabolic syndrome type 2 diabetes mellitus DM hyperlipidemia and obesity Insulin resistance is considered one of the first steps to developing fatty liver infiltration Indeed 70 to 80 of patients with diabetes have NASH A recent change in nomenclature now accounts for the link with cardiometabolic criteria NAFLD is now MASLD metabolic dysfunction-associated steatotic liver disease ie steatosis and at least 1 cardiometabolic factor and NASH is MASH metabolic dysfunction-associated steatohepatitis ie MASLD with inflammation regrouped as steatotic liver disease SLD
SLD is a silent disease patients have no symptoms are not routinely screened for the disease and SLD is often revealed through complications of cirrhosis at a late stage for intervention Inflammation is confirmed when liver function tests alanine aminotransferase ALT and aspartate aminotransferase AST are elevated It is recommended to assess the level of associated fibrosis through non-invasive tests such as elastography that evaluates liver stiffness that increases with fibrosis or algorithms such as Fibrosis-4 FIB-4 that combines age ALT AST and platelets count to identify fibrosis in patients over 35 years old The SLD burden is expected to increase An estimated 30 of the population worldwide has MASLD and 5 of Canadians have MASH 2 A Canadian study concluded that the number of people with post-MASH decompensated cirrhosis will double by 2030 and cases of liver cancer will increase by 80 2 MASH is a leading cause of liver transplantation in Canada 2 Despite extensive research with currently over 1350 active clinical trials clinicaltrialsgov accessed 19092023 there is no cure for SLD and the treatment relies on diet weight loss and physical activity PA The current North American guidelines state that patients with NAFLD should be strongly encouraged to engage in PA to the extent possible
The effects of PA on SLD have been studied extensively A systematic review 3 showed personalized PA improved the quality of life for cirrhotic patients without significant side effects and may reduce the 90-day readmission rates for transplant patients at the end of the program Henri et al showed US NAFLD adults who engaged in vigorous PA have a lower risk of death from cancer and all causes than NAFLD adults who do not engage in any PA benefits persisted for low PA and any PA versus no PA 4 Similarly a US study showed PA is inversely associated with NALFD and associated with better survival for NALFD patients 5 PA is also successful in preventing DM which is now included in the MASH definition 6 Moreover meta-analyses have concluded that PA contributes to decreasing levels of various biological markers of SLD 7 8 and inflammatory markers 9 thus reducing intra-hepatic fat 10 11 12 13 PA is thus efficacious in reducing inflammation and fibrosis in patients with SLD However key knowledge gaps remain including 1 scarce data on the impact of sustained PA in MASH patients especially post-participation in studies 2 lack of consistency in terms of eligibility criteria that are often too narrow and exclude patients seen in practice 3 heterogeneous PA parameters eg dosage type duration and 4 variability of biological data collected It is thus difficult to precisely define through meta-analyses andor systematic reviews the optimal program to help support PA or its duration Another critical gap is what is the influence of interventions that aim to have patients initiate and maintain PA on their own This is important because in reality it is not possible or sustainable to offer patients supervised PA sessions in the amount that is commensurate with current PA guidelines considering patients have their own barriers to PA and the lack of support to help them initiate and maintain PA in everyday life Indeed from discussions with patients during clinical evaluation with Dr Fresne some barriers are lack of time insufficient knowledge fear of injury and lack of financial resources In the literature perceived lack of resources and education physical discomfort or limitations or pain lack of space and time constraints have been identified as barriers for PA 1314 15
We believe individualized support and guidance to help patients progressively engage in more PA is a better results-oriented sustainable approach than delivering supervised PA training sessions and propose a personalized counselling intervention to engage patients with SLD in PA
Additionally whether having patients initiate and maintain PA in everyday life by providing them with support can contribute to reducing inflammation andor fibrosis in the liver remains to be described It is known that sarcopenia loss of skeletal muscle mass and strength is associated with cirrhosisliver fibrosis and DM suggesting communication between the liver and muscles During PA the muscle secretes small peptides called myokines that act on the skeletal muscle but also on distant organs to improve their function including decreasing inflammation and liver lipid content such as interleukin 6 IL-6 IL-15 irisin 16 PA also modifies the secretion of hepatokines peptides secreted by hepatocytes It is therefore possible that levels of these proteins will be modified in our population if they can initiate and maintain PA during their participation in PA counselling compared to their baseline PA level These proteins could therefore serve as biomarkers to determine the efficacy of the PA counselling in improving SLD and reducing inflammation
Significance and Innovation
Engaging SLD patients in PA is crucial and a matter of public health The number of SLD patients will increase in the next 10 years and there is currently no medication to treat the condition nor prevent the evolution towards cirrhosis with the associated risk of liver transplant and cancer PA has proven its efficacy in SLD However physicians may not know how to help their patients to practice PA as a treatment and SLD patients face barriers to PA that need better characterization We believe our innovative PA intervention using personalized counselling could help patients to overcome their barriers to PA To our knowledge this would be the first study that would provide patients keys to successfully engage in PA and empower SLD patients with PA through counselling We believe participants in our study will be more likely to maintain long-term PA and the project will help us understand the barriers and facilitators to PA behavior change faced by SLD patients If this feasibility project proves successful we will develop a larger trial to assess the long-term engagement of SLD patients in PA and study the effects of PA on the interaction between liver fat and muscle in SLD patients
Population and recruitment Based on past SCED studies our sample size will be 12 participants They will be recruited through the hepatology clinic at Hôpital Montfort
Intervention The intervention is informed by the Telehealth Bariatric Behavioral Intervention TELE-BariACTIV study led by Drs Baillot and Brunet 18 The TELE-BariACTIV has been developed to increase PA for patients awaiting bariatric surgery It is based on the principles of the BariACTIV trials 1920 that demonstrated a 6-week period of personalized face-to-face counselling before surgery centered on behavioral strategies such as goal-setting and self-monitoring significantly increased pre-surgery moderate-to-vigourous PA TELE-BariACTIV was designed to reinforce theory-based content and participants perspective and include telehealth to increase reach It was successfully tested article in preparation using a SCED The purpose of the intervention is to increase autonomy motivation and self-confidence so participants can autonomously engage in PA The content of the TELE-BariACTIV counselling is meant to be adapted to reflect participants conditions and we will do so by working with a patient-partner The intervention aims to increase motivation via satisfaction of basic psychological needs and self-efficacy critical determinants of PA behavior change
Data collection We will collect sociodemographic data such as age sex gender language level of education profession and income PA will be measured daily throughout the trial via an accelerometer 7-14 days in each A phase mailed to the participants They will be instructed to wear the accelerometer continuously except during water-based activities and to maintain a log of wear times with waking and bed times Accelerometer data will be extracted and downloaded 10-second epochs using the appropriate software and will be cleaned in accordance with the logbooks provided by the participants
Qualitative data We will collect data on 1 participants opinions of the trial assessments timing etc and intervention via with a semi-structured interview at the end of their participation 2 onacceptability with a 7-item questionnaire developed and validated by the research team and 3 on PA counsellor notes for each intervention session for examples duration topics discussed accomplishment of session objectives participants reactions to the content next steps with the participants and reflections as a PA counsellor eg problems arising during the sessions overall experience delivering the session suggestion for intervention or personal improvements and session deviations
Quantitative data We will collectmeasure pre and post intervention data for liver function tests ALT AST Gamma Glutamyl Transferase Alkaline Phosphatase bilirubin albumin totalHigh Density LipoproteinLow Density Lipoprotein cholesterol levels triglycerides levels fasting glucose and insulin HbA1c fasting free fatty acids Body Mass Index waist circumference IL-6 TNF-α CReactive Protein and leptin and calculate composite scores such as FIB-4 We will also evaluate liver fibrosis with a liver elastography before screening and at the end of participation Myokines and hepatokines will be measured using available kits
Data analysis
Quantitative data Descriptive statistics will be computed for baseline sociodemographic clinical biological feasibility and acceptability data derived from the numerical responses and close-ended questions All statistical analyses will be carried out using R and the appropriate packages A Tau-U test for each participant and for the group will be performed to compare daily PA based on accelerometer data between phases A1 and B as well as A1 and A2 Individual effect sizes will be aggregated in a meta-analysis to obtain a group-based effect size A sensitivity analysis will also be performed with a randomization test
Qualitative data The content of the interviews and the PA counselors notes completed after the sessions will be analyzed by two team members using content analysis after verbatim transcription using the NVivo software
Based on data from the TELE-bariACTIV study our project will be deemed successful if the refusal rate is 25 the retention rate after phase B PA intervention is 75 the intervention attendance rate is 75 and the intervention attrition rate 25 The main objectives of our project are feasibility and acceptability at this point the evolution or lack of evolution of biological or imaging markers before and after participation will not be considered for the success of the project It will however help define which markers should be used for a large-scale trial
Liver steatosis is the build-up of fat in the form of lipid droplets inside hepatocytes liver cells Although it is a form of energy storage it is considered pathological when more than 5 of hepatocytes demonstrate fat infiltration on a liver biopsy or imaging ultrasound magnetic resonance or computed tomography Until recently liver steatosis was described as two entities with a clinicopathological continuum non-alcoholic fatty liver disease NAFLD and non-alcoholic steatohepatitis NASH ie NAFLD with inflammation NAFLDNASH is strongly associated with features of the metabolic syndrome type 2 diabetes mellitus DM hyperlipidemia and obesity Insulin resistance is considered one of the first steps to developing fatty liver infiltration Indeed 70 to 80 of patients with diabetes have NASH A recent change in nomenclature now accounts for the link with cardiometabolic criteria NAFLD is now MASLD metabolic dysfunction-associated steatotic liver disease ie steatosis and at least 1 cardiometabolic factor and NASH is MASH metabolic dysfunction-associated steatohepatitis ie MASLD with inflammation regrouped as steatotic liver disease SLD
SLD is a silent disease patients have no symptoms are not routinely screened for the disease and SLD is often revealed through complications of cirrhosis at a late stage for intervention Inflammation is confirmed when liver function tests alanine aminotransferase ALT and aspartate aminotransferase AST are elevated It is recommended to assess the level of associated fibrosis through non-invasive tests such as elastography that evaluates liver stiffness that increases with fibrosis or algorithms such as Fibrosis-4 FIB-4 that combines age ALT AST and platelets count to identify fibrosis in patients over 35 years old The SLD burden is expected to increase An estimated 30 of the population worldwide has MASLD and 5 of Canadians have MASH 2 A Canadian study concluded that the number of people with post-MASH decompensated cirrhosis will double by 2030 and cases of liver cancer will increase by 80 2 MASH is a leading cause of liver transplantation in Canada 2 Despite extensive research with currently over 1350 active clinical trials clinicaltrialsgov accessed 19092023 there is no cure for SLD and the treatment relies on diet weight loss and physical activity PA The current North American guidelines state that patients with NAFLD should be strongly encouraged to engage in PA to the extent possible
The effects of PA on SLD have been studied extensively A systematic review 3 showed personalized PA improved the quality of life for cirrhotic patients without significant side effects and may reduce the 90-day readmission rates for transplant patients at the end of the program Henri et al showed US NAFLD adults who engaged in vigorous PA have a lower risk of death from cancer and all causes than NAFLD adults who do not engage in any PA benefits persisted for low PA and any PA versus no PA 4 Similarly a US study showed PA is inversely associated with NALFD and associated with better survival for NALFD patients 5 PA is also successful in preventing DM which is now included in the MASH definition 6 Moreover meta-analyses have concluded that PA contributes to decreasing levels of various biological markers of SLD 7 8 and inflammatory markers 9 thus reducing intra-hepatic fat 10 11 12 13 PA is thus efficacious in reducing inflammation and fibrosis in patients with SLD However key knowledge gaps remain including 1 scarce data on the impact of sustained PA in MASH patients especially post-participation in studies 2 lack of consistency in terms of eligibility criteria that are often too narrow and exclude patients seen in practice 3 heterogeneous PA parameters eg dosage type duration and 4 variability of biological data collected It is thus difficult to precisely define through meta-analyses andor systematic reviews the optimal program to help support PA or its duration Another critical gap is what is the influence of interventions that aim to have patients initiate and maintain PA on their own This is important because in reality it is not possible or sustainable to offer patients supervised PA sessions in the amount that is commensurate with current PA guidelines considering patients have their own barriers to PA and the lack of support to help them initiate and maintain PA in everyday life Indeed from discussions with patients during clinical evaluation with Dr Fresne some barriers are lack of time insufficient knowledge fear of injury and lack of financial resources In the literature perceived lack of resources and education physical discomfort or limitations or pain lack of space and time constraints have been identified as barriers for PA 1314 15
We believe individualized support and guidance to help patients progressively engage in more PA is a better results-oriented sustainable approach than delivering supervised PA training sessions and propose a personalized counselling intervention to engage patients with SLD in PA
Additionally whether having patients initiate and maintain PA in everyday life by providing them with support can contribute to reducing inflammation andor fibrosis in the liver remains to be described It is known that sarcopenia loss of skeletal muscle mass and strength is associated with cirrhosisliver fibrosis and DM suggesting communication between the liver and muscles During PA the muscle secretes small peptides called myokines that act on the skeletal muscle but also on distant organs to improve their function including decreasing inflammation and liver lipid content such as interleukin 6 IL-6 IL-15 irisin 16 PA also modifies the secretion of hepatokines peptides secreted by hepatocytes It is therefore possible that levels of these proteins will be modified in our population if they can initiate and maintain PA during their participation in PA counselling compared to their baseline PA level These proteins could therefore serve as biomarkers to determine the efficacy of the PA counselling in improving SLD and reducing inflammation
Significance and Innovation
Engaging SLD patients in PA is crucial and a matter of public health The number of SLD patients will increase in the next 10 years and there is currently no medication to treat the condition nor prevent the evolution towards cirrhosis with the associated risk of liver transplant and cancer PA has proven its efficacy in SLD However physicians may not know how to help their patients to practice PA as a treatment and SLD patients face barriers to PA that need better characterization We believe our innovative PA intervention using personalized counselling could help patients to overcome their barriers to PA To our knowledge this would be the first study that would provide patients keys to successfully engage in PA and empower SLD patients with PA through counselling We believe participants in our study will be more likely to maintain long-term PA and the project will help us understand the barriers and facilitators to PA behavior change faced by SLD patients If this feasibility project proves successful we will develop a larger trial to assess the long-term engagement of SLD patients in PA and study the effects of PA on the interaction between liver fat and muscle in SLD patients
Population and recruitment Based on past SCED studies our sample size will be 12 participants They will be recruited through the hepatology clinic at Hôpital Montfort
Intervention The intervention is informed by the Telehealth Bariatric Behavioral Intervention TELE-BariACTIV study led by Drs Baillot and Brunet 18 The TELE-BariACTIV has been developed to increase PA for patients awaiting bariatric surgery It is based on the principles of the BariACTIV trials 1920 that demonstrated a 6-week period of personalized face-to-face counselling before surgery centered on behavioral strategies such as goal-setting and self-monitoring significantly increased pre-surgery moderate-to-vigourous PA TELE-BariACTIV was designed to reinforce theory-based content and participants perspective and include telehealth to increase reach It was successfully tested article in preparation using a SCED The purpose of the intervention is to increase autonomy motivation and self-confidence so participants can autonomously engage in PA The content of the TELE-BariACTIV counselling is meant to be adapted to reflect participants conditions and we will do so by working with a patient-partner The intervention aims to increase motivation via satisfaction of basic psychological needs and self-efficacy critical determinants of PA behavior change
Data collection We will collect sociodemographic data such as age sex gender language level of education profession and income PA will be measured daily throughout the trial via an accelerometer 7-14 days in each A phase mailed to the participants They will be instructed to wear the accelerometer continuously except during water-based activities and to maintain a log of wear times with waking and bed times Accelerometer data will be extracted and downloaded 10-second epochs using the appropriate software and will be cleaned in accordance with the logbooks provided by the participants
Qualitative data We will collect data on 1 participants opinions of the trial assessments timing etc and intervention via with a semi-structured interview at the end of their participation 2 onacceptability with a 7-item questionnaire developed and validated by the research team and 3 on PA counsellor notes for each intervention session for examples duration topics discussed accomplishment of session objectives participants reactions to the content next steps with the participants and reflections as a PA counsellor eg problems arising during the sessions overall experience delivering the session suggestion for intervention or personal improvements and session deviations
Quantitative data We will collectmeasure pre and post intervention data for liver function tests ALT AST Gamma Glutamyl Transferase Alkaline Phosphatase bilirubin albumin totalHigh Density LipoproteinLow Density Lipoprotein cholesterol levels triglycerides levels fasting glucose and insulin HbA1c fasting free fatty acids Body Mass Index waist circumference IL-6 TNF-α CReactive Protein and leptin and calculate composite scores such as FIB-4 We will also evaluate liver fibrosis with a liver elastography before screening and at the end of participation Myokines and hepatokines will be measured using available kits
Data analysis
Quantitative data Descriptive statistics will be computed for baseline sociodemographic clinical biological feasibility and acceptability data derived from the numerical responses and close-ended questions All statistical analyses will be carried out using R and the appropriate packages A Tau-U test for each participant and for the group will be performed to compare daily PA based on accelerometer data between phases A1 and B as well as A1 and A2 Individual effect sizes will be aggregated in a meta-analysis to obtain a group-based effect size A sensitivity analysis will also be performed with a randomization test
Qualitative data The content of the interviews and the PA counselors notes completed after the sessions will be analyzed by two team members using content analysis after verbatim transcription using the NVivo software
Based on data from the TELE-bariACTIV study our project will be deemed successful if the refusal rate is 25 the retention rate after phase B PA intervention is 75 the intervention attendance rate is 75 and the intervention attrition rate 25 The main objectives of our project are feasibility and acceptability at this point the evolution or lack of evolution of biological or imaging markers before and after participation will not be considered for the success of the project It will however help define which markers should be used for a large-scale trial
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None