Modifying Adiposity Through Behavioral Strategies to Improve COVID-19 Rehabilitation

Study Overview
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Brief Summary
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The research in this VA Merit will examine the effects of obesity and Post-COVID Conditions (PCC) on physical functioning, health-related quality of life, and adipose tissue inflammatory and cellular senescence profiles in older Veterans. Further, it will evaluate whether a weight loss intervention, including dietary modification and exercise, in obese Veterans with and without PCC will reduce systemic and adipose tissue inflammation and senescence and promote PCC recovery.

Detailed Description
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Findings of post-acute sequelae of Post-COVID Conditions (PCC) manifestations of fatigue, pain, dyspnea, and muscle weakness, provide a strong rationale for rehabilitation; yet few formal studies exist and the effects of severe acute respiratory syndrome coronavirus-2 infection on function are not well described. Notably, two-thirds of Veterans are overweight and obese, rendering excess adiposity a significant risk factor and a high-priority area related to PCC prevention and care. Obesity increases the risk of severe illness in Veterans recovering from PCC, but how it does so is not fully understood. Recent research suggests that excess adipose tissue is associated with adverse changes in adipose cellular function, and that these variations may be involved in the biology of aging and the etiology of aging-related diseases. Adipose tissue contains cells that have undergone cellular senescence, which induces inflammation, cytotoxicity, and metabolic dysfunction in other cells and tissues. However, the precise role of adipose tissue cellular composition on PCC recovery is limited. Thus, the investigators propose to evaluate the role of obesity and PCC on physical functioning, health-related quality of life (HRQOL), and systemic and adipose tissue inflammatory and cellular senescence profiles in ethnically diverse older Veterans from the Audie Murphy (San Antonio) and Baltimore VA Medical Centers. Further, the investigators propose a randomized controlled trial to determine whether a reduction in body weight and increased physical function by a weight loss intervention (WL), including dietary modification and exercise, in obese Veterans with PCC will reduce systemic and adipose tissue inflammation and senescence, which will have important implications for PCC recovery.

Official Title
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Modifying Adiposity Through Behavioral Strategies to Improve COVID-19 Rehabilitation

Conditions
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Post-COVID Conditions, Obesity

Intervention / Treatment
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* Behavioral: 12-weeks of Weight Loss
* Behavioral: 12-weeks of Weight Stability


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: U.S. Veteran No Post-COVID symptoms or at least one Post-COVID symptom lasting >4 weeks Body Mass Index: 19-25 or 30-40 kg/m2 Postmenopausal status for women Exclusion Criteria: Neurologic, musculoskeletal, or other condition that limits subject's ability to complete study physical assessments Active inflammatory, COVID-19, autoimmune, infectious, hepatic (LFTs > 2.5 x WNL), renal (eGFR<45), gastrointestinal, malignant, and psychiatric disease Uncontrolled diabetes (HbA1c >10% or the current use of insulin) Weight change within the past month of >5 kg History of keloid formation Self-reported alcohol or drug abuse Anti-coagulant medication usage

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Weight Loss Program (Diet and Exercise)
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Weight Loss<br>Participants will be asked to participate in a 1x/week center-based nutrition diet class, 2x/week center-based exercise classes, and 1x/week exercise session conducted on their own for 12 weeks. | Behavioral: 12-weeks of Weight Loss<br>* Participants will be asked to participate in a 1x/week center-based nutrition diet class, 2x/week center-based exercise classes, and 1x/week exercise session conducted on their own for 12 weeks.<br>|
| Active Comparator: Weight Stability<br>Participants will be asked to participate in a 1x/week center-based health education class, 2x/week center-based stretching/balance classes, and 1x/week stretching/balance session conducted on their own for 12 weeks. | Behavioral: 12-weeks of Weight Stability<br>* Participants will be asked to participate in a 1x/week center-based health education class, 2x/week center-based stretching/balance classes, and 1x/week stretching/balance session conducted on their own for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiorespiratory Fitness (VO2max) | VO2max (ml/kg/min) comparison between lean PCC naïve, lean with PCC, obese PCC naïve, and obese with PCC | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cardiorespiratory Fitness (VO2max) | Change in VO2max (L/min) | Baseline, After 12 weeks of Weight Loss | 
| Change in adipose tissue cellular senescence | Change in adipose tissue chemokine (C-C motif) ligand 3 (CCL3) | Baseline, After 12 weeks of Weight Loss | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Obesity, Senescence, Weight Loss, Exercise