Restoring Energy With Sub-symptom Threshold Optimized Rehabilitation Exercise for Long COVID

Long Covid19 Clinical Trial

— RESToRE  

Official title:

RESToRE: Restoring Energy With Sub-symptom Threshold Optimized Rehabilitation Exercise for Long COVID

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06172803
• Other study ID #: AAAU4504 (Aim 1)
• Status: Completed
• Phase: N/A
• Start date: October 1, 2023
• Est. completion date: January 15, 2024

Study information

• Verified date: June 2024
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The overall goal of this study is to find out if rehabilitation exercise can help people who have long COVID. Participants will be randomized by chance to receive either aerobic exercise or breathing exercise (combined with stretches). Participants will be guided and supported in completing a tailored, 6-week home exercise program to be performed 5 - 6 days a week, prescribed and supervised by rehabilitation therapists. Participants will perform breathing exercises, which will be supervised by an occupational therapist. The focus of Aim 1 is to determine feasibility of implementing RESToRE in long COVID.

Description:

Long COVID, also known as post-acute coronavirus 2019 syndrome, is characterized by debilitating, multi-organ symptoms beyond 3 months from the onset of acute illness, consistent with autonomic nervous system dysfunction. Prevalence estimate of long COVID is 10

• 20% of survivors of COVID-19, representing about 10-20 million global long-term cases. Multi-organ, autonomic-related symptoms of long COVID, such as exhausting fatigue and post-exertional malaise, are remarkably like post-concussion syndrome and chronic fatigue syndrome. Post-exertional malaise, likely a cardinal symptom of long COVID, is "an exacerbation of some or all of an individual's symptoms after physical or cognitive exertion, or orthostatic stress", significantly impacting functional ability and quality of life. This abnormal response to exertion is often described as "flu-like" and typically includes brain fog. Common "long hauler" symptoms reported in our cohort of patients with long COVID (n=30) were fatigue (>70%), symptoms of dysautonomia (80%, primarily orthostasis), "brain fog" (100%), and new or worse mood symptoms (90%), especially anxiety. Experience from Severe Acute Respiratory Syndrome (SARS-CoV-1) notably showed that survivors suffered chronic fatigue and mental illnesses 4 years after acute viral illness. Rehabilitation studies in coronavirus disease (Covid-19) have targeted sub-acute lung sequelae of Covid-19 rather than post-acute sequalae of long COVID. This study addresses the World Health Organization's urgent call for rehabilitation research for long COVID.

The investigators identified blunted rise in heart rate (HR), called chronotropic intolerance, during maximal cardiopulmonary exercise testing (CPET) in 19 adults with long COVID. Chronotropic intolerance is defined as inability to meet 80% of age-derived heart rate, HR peak. Group HR peak mean (SD) was 69 (7.7) % predicted. This blunted rise in HR is associated with post-exertional malaise, similar to the pattern of symptoms in post-concussion syndrome and chronic fatigue syndrome, which share underlying autonomic nervous system (ANS) dysfunction and impaired cerebral blood flow regulation. The investigators identified a need for more comprehensive and precise measurement of post-exertional malaise in long COVID. In a randomized controlled trial (RCT), the investigators also tested a sub-symptom threshold aerobic exercise program, focused on treating persisting symptoms of post-concussion syndrome. The investigators found this aerobic exercise program reduced persistent symptoms of exercise intolerance, fatigue, and dysautonomia more quickly in subjects compared with a control group of stretching exercises (n=103).

Informed by research in post-concussion syndrome, the investigators are proposing a two-arm randomized controlled trial (RCT) to study the feasibility of an exercise program called, Restoring Energy with Sub-symptom Threshold Aerobic Rehabilitation Exercise (RESToRE). The central hypothesis is that restoration of autonomic control through RESToRE will resolve persisting symptoms of long COVID faster compared with placebo-like stretching and breathing exercise (without rise in HR). RESToRE is an interdisciplinary, hybrid 8-week intervention consisting of three core components: (1) home-based aerobic exercise, of 20 minutes most days, with HR monitoring at 70-80% of the HR threshold at which symptoms increase, (2) phone-based motivational exercise coaching, 20 minutes weekly; and (3) supervised exercise with an exercise physiologist, twice-monthly in the clinic. Key to RESToRE's feasibility is its telehealth component, including Apple watch and app for HR fidelity monitoring, PhysiTrack's exercise library app, and LifeData dashboard for real-time post-exertional malaise and remote exercise monitoring. Our long-term goal is to establish an efficacious exercise program to speed recovery from long COVID.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4
• Est. completion date: January 15, 2024
• Est. primary completion date: January 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• English speaking

• Age of 21 years or older

• Diagnosis of long COVID

• Score >0 on energy, daily activities, sleep, chest tightness, or breathlessness on COPD Assessment Test or self-reported brain fog

• Able to use a smartphone.

Exclusion Criteria:

• >70years old due to risk of sarcopenia

• Frailty defined as gait speed <1 m/s on 4- Meter Gait Speed (4MGS) test due to falls risk

• Diagnosis of chronic cardiac or pulmonary disease, including atrial fibrillation, ME/CFS, post-concussion syndrome, chronic Lyme disease, lupus, or sarcopenia comorbidities (due to PEM and/or fatigue)

• Medical history of ICU stay for COVID-19 illness due to risk of post-ICU syndrome and increased rehabilitation needs

• Inability to ambulate independently and safely without a walking aide

• Diagnosis of dementia or neurodegenerative disease, multiple sclerosis, or rheumatoid arthritis with associated cognitive dysfunction or fatigue.

Related Conditions & MeSH terms

• Exercise Intolerance

Intervention

Behavioral:
• Restoring Energy with Sub-symptom Threshold Aerobic Rehabilitation Exercise
8 week exercise program. 20 minutes of home aerobic exercise most days, phone- based motivational exercise coaching and supervised exercise with our team exercise physiologist.
• Light Stretching/Breathing Exercises
The control group will receive 8-week, attention-matched, stretching and breathing exercises, supervised by a rehabilitation clinician (via 20-minute weekly video visits). Exercises performed 5 days a week will not increase HR significantly. Participants will record and track their HR with Apple watch and app; like RESToRE, fidelity of treatment will be objectively measured using HR data.

Locations

Country	Name	City	State
United States	Columbia University Irving Medical Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Columbia University	New York University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants who enrolled	Feasibility of the RESToRE program will be determined by measuring the number of participants who enroll.	10 weeks
Primary	Number of participants who completed	Feasibility of the RESToRE program will be determined by measuring the number of participants who complete (participated through the end of the study).	10 weeks
Primary	Number of participants who adhered to session attendance	Feasibility of the RESToRE program will be determined by measuring the number of participants who achieve =80% exercise adherence and session attendance.	10 weeks
Secondary	PROMIS-29 scale score	This toll/questionnaire is designed to measure participants quality of life. Score range is 1-5, with higher score correlating to worse outcomes.	baseline and post intervention at 8 weeks
Secondary	Rand 36-Item Health Survey (SF-36) score	This survey evaluates participants mental and physical health with 8 scales aggregated. Score range is 1-6, with the higher score correlating to worse overall health outcomes.	Baseline and Post Intervention at 8 weeks
Secondary	VO2 % predicted from Cardiopulmonary Exercise Testing (CPET)	VO2 % predicted (oxygen consumption) based on normative data. Participants' scores will be compared to norms for assessing exercise ability. Group means will be compared.	Baseline and post intervention at 8 weeks
Secondary	Number of participants with orthostatic hypocapnia.	The Nasa Lean Test: Participants will stand and lean against a wall with shoulder blades touching and heels 6 - 8 inches from the wall for 10 minutes. HR, BP, SpO2, ETCO2, and symptoms will be recorded in standing leaning posture every minute for 10 mins. Capnography will be used to identify orthostatic hypocapnia.	baseline and post intervention at 8 weeks
Secondary	EuroQol: Education Quotient-5D Visual Analogue Scale score	This is to measure quality of life. Score range is 0-100, with 100 being the best health you can imagine and 0 being the worst health.	baseline and post intervention at 8 weeks
Secondary	General Symptom Questionnaire (SGQ-30) score	This is to assess participants symptoms regarding pain/fatigue, psychiatric, neurological, and viral-like. Score range is 0 which is not at all to 4 which is very much. Higher score represents worst symptoms.	baseline and post intervention at 8 weeks
Secondary	PROMIS Cognitive Function score	This is an 8-item Short Form, measuring perceived difficulties in cognition (e.g., attention, concentration, executive functioning). Score range is 1-5. 1 is very often to 5 which is never. The higher score is better.	baseline and post intervention at 8 weeks
Secondary	Global Change Assessment (GCA) score	This is to measure patients change of symptoms in terms of physical function and fatigue throughout the study. Score range is -7 to 7. -7 is a very great deal worse and 7 is a great deal better. The higher the score the better.	baseline and post intervention at 8 weeks