An OBServational Clinical Trial (SARA-OBS) in Sarcopenia and Sarcopenic Obesity in Patients Aged 65 Years and Over

Study Overview
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Brief Summary
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The SARA-OBS is a single arm phase 2 clinical trial, with no investigational product and no therapeutic intervention that will be conducted in three European countries, (Belgium, France and Italy), and in the US. 300 community dwelling older adults (men or women≥65 years) reporting loss of physical function and at risk of mobility disability, will undergo mobility functional evaluation and Dual-energy X-ray Absorptiometry DXA scan for body composition determination twice, at six-month interval. Participants aged ≥ 65 years complaining of poor physical function will be selected to perform SPPB (Short Physical Performance Battery)tests. Those with SPPB scores ≤ 8/12 will be selected to perform body composition analysis with DXA Scan. Participants with ALM/BMI < 0.789 in men and 0.512 in women will be included. The investigational phase will comprise two main visits: the inclusion visit and the 6-month visit. Both the 6-minute walk distance test and the 400-metre walking test will be administered at the main visits. Patient Reported Outcomes (PROs) will be completed by the patients at the same visits.

Detailed Description
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The SARA-OBS is a phase 2 clinical trial, with no investigational product and no therapeutic intervention. It will be conducted in three European countries, Belgium, France and Italy, and in the US. 300 community dwelling older adults (men or women≥65 years) reporting loss of physical function and at risk of mobility disability, will undergo mobility functional evaluation and Dual-energy X-ray Absorptiometry DXA scan for body composition determination twice, at six-month interval. The general objective is to characterise sarcopenia including sarcopenic obesity in a population of older persons living in the community and at risk of mobility disability; evaluate their physical performance and body composition in view of the design of a phase 2 clinical study on the efficacy and safety of BIO101 on the prevention of mobility disability in the at-risk community dwelling older adults (≥65 years) reporting loss of physical function. The primary objective characterise sarcopenia including sarcopenic obesity, in older persons at risk of mobility disability. Sarcopenia will be defined according to the criteria of the Foundation of NIH; the risk of mobility disability will be operationalised by the Short Physical Performance Battery (SPPB). For this purpose, the 6-minute walking distance and the 400-meter walking test will be evaluated at 6-month intervals, in the absence of any therapeutic intervention. The incident rate of change will be estimated on the sample and pre-specified subgroups (e.g. gender, SPPB baseline score, etc.). Two important Secondary Objectives are also included : To evaluate muscle strength (handgrip/knee extension) and stair power climbing test To evaluate self-administered quality-of-life tests as putative patient reported outcomes (PROs): Short Form Health Survey (SF-36) and Sarcopenia Quality of Life (SarQol) for all subjects; in addition, TSD-OC for participants with BMI≥30 Exploratory objectives are : To measure tentative biomarkers of sarcopenia and poor physical performance, and test their correlation with physical function change over the study observation. To record actimetry via a connected wearable device, in order to describe daily physical activity and possibly identify patterns predictive of improvement/worsening of physical function. Primary endpoints are the 6-minute Walk Test/400m Walking Test and Co-Primary endpoints are SF-36 and SarQoL for all subjects; additionally TSD-OC for subjects with BMI ≥ 30.

Official Title
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Characterising SARcopenia and Sarcopenic Obesity in Patients Aged 65 Years and Over at Risk of Mobility Disability. An OBServational Clinical Trial (SARA-OBS)

Conditions
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Muscle Weakness, Sarcopenia, Gait Disorders in Old Age

Intervention / Treatment
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* Other: No Drug and no aspecific intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged ≥ 65 years and living in the community, reporting loss of physical function Short Physical Performance Battery (SPPB) score ≤ 8 ALM/BMI < 0.789 in men and 0.512 in women, by DXA scan Exclusion Criteria: Unable or unwilling to provide informed consent Unable to understand and perform the functional tests, as judged by the Investigator Current treatment with anabolic drugs, i.e. testosterone Clinical conditions: Current diagnosis major psychiatric disorders. Alcohol abuse or dependence Severe arthritis Cancer requiring active treatment Lung disease requiring regular use of supplemental oxygen Inflammatory conditions requiring regular use of oral or parenteral corticosteroid agents Severe cardiovascular disease (including New York Heart Association [NYHA] class III or IV congestive heart failure, clinically significant valvular disease, history of cardiac arrest, presence of an implantable defibrillator, or uncontrolled angina) Parkinson's disease or other progressive neurological disorder Renal disease requiring dialysis Chest pain, severe shortness of breath, or occurrence of other safety concerns during the baseline the 6MWT, or the 400-meter walk test Current physical/rehabilitation therapy Current enrolment in another clinical trial Concomitant condition implying life expectancy ≤ 6 months Any other condition precluding the regular participation to the clinical trial, as judged by the Investigator.

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 95 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: No Drug and no aspecific intervention|No intervention|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6-minute or 400 meters walk. | The 6 minutes walking distance is a functional exercise capacity test that involves measuring the distance covered by a participant within a specified time of 6 minutes. The 400 meter walking test is a measure of how long it will take for a volunteer to complete the specified 400 meters distance. | Change from Baseline 6 minute or 400 meters to measurement at 6 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SPPB | Physical performance tests corresponding to standing balance, walking speed and chair stand will be assessed | Change from Baseline SPPB to measurement at 6 months. | 
| DEXA | Body composition especially Lean Body Mass and Fat Mass will be measured. This will allow definition of the appendicular Lean Body mass. | Change from Baseline DEXA to measurement at 6 months. | 
| Stair Climb Power Test | The ability to ascend and descend stairs (9 stairs of 20 cm height) will be assessed in a specific period of time | Change from Baseline Stair Climb Power Test to measurement at 6 months. | 
| Actimetry | The continuous physical activity of the volunteers will be recorded using a specific device during the 6-month study period. | Change from actimetry at Month1 to measurement at 6 months. | 
| Grip strength | The grip strength will be measured using the appropriate dynamometer. Strength will be measured 3 times for both hands and the highest value will be kept for further analysis. | Change from Baseline Grip Strength to measurement at 6 months. | 
| Knee extension | The knee extension measurement will be performed using isokinetic dynamometer. | Change from Baseline knee extension to measurement at 6 months. | 
| Patient Reported Outcome : SF-36 | Electronically self administrated Patient Reported Outcome SF-36 will be assessed a SF-36 questionnaire. | Change from Baseline Patient Reported Outcome to measurement at 6 months. | 
| Patient Reported Outcomes : SarQoL | Electronically self administrated Patient Reported Outcome SarQoL will be assessed through the SarQoL questionnaire. | Change from Baseline Patient Reported Outcome to measurement at 6 months. | 
| Patient Reported Outcomes TSC-OD for patients with BMI>30 | Electronically self administrated Patient Reported Outcomes will be assessed through the TSD-OC questionnaire for volunteers having BMI>30 | Change from Baseline Patient Reported Outcome to measurement at 6 months. | 
| Patient Reported Outcomes (PAT-D) | Electronically administrated Patient Reported Outcome will be assessed with assistance of the investigator through the PAT-D questionnaire. | Change from Baseline Patient Reported Outcome to measurement at 6 months. | 
| Biomarkers | Biomarkers specific to Sarcopenia and to the Renin Angiotensin System ( Aldosterone; Renin; Myostatin; PIIINP; IL-6; hsCRP etc....) will be measured at baseline and at 6 months. | Change from Baseline Biomarkers to measurement at 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sarcopenia, Sarcopenic Obesity, observational study, 6-minute walking distance, 400 meters walking test, Patient Reported Outcomes