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

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.

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 :

1. To evaluate muscle strength (handgrip/knee extension) and stair power climbing test
2. 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 :

1. To measure tentative biomarkers of sarcopenia and poor physical performance, and test their correlation with physical function change over the study observation.
2. 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.

Eligibility Criteria:
Inclusion Criteria:

1. Men and women aged ≥ 65 years and living in the community, reporting loss of physical function
2. Short Physical Performance Battery (SPPB) score ≤ 8
3. ALM/BMI \< 0.789 in men and 0.512 in women, by DXA scan

Exclusion Criteria:

1. Unable or unwilling to provide informed consent
2. Unable to understand and perform the functional tests, as judged by the Investigator
3. Current treatment with anabolic drugs, i.e. testosterone
4. Clinical conditions:

   1. Current diagnosis major psychiatric disorders.
   2. Alcohol abuse or dependence
   3. Severe arthritis
   4. Cancer requiring active treatment
   5. Lung disease requiring regular use of supplemental oxygen
   6. Inflammatory conditions requiring regular use of oral or parenteral corticosteroid agents
   7. 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)
   8. Parkinson's disease or other progressive neurological disorder
   9. Renal disease requiring dialysis
   10. Chest pain, severe shortness of breath, or occurrence of other safety concerns during the baseline the 6MWT, or the 400-meter walk test
5. Current physical/rehabilitation therapy
6. Current enrolment in another clinical trial
7. Concomitant condition implying life expectancy ≤ 6 months
8. Any other condition precluding the regular participation to the clinical trial, as judged by the Investigator.