Resistive Training Combined With Nutritional Therapy After Stroke (REPS)

Stroke survivors experience severe muscle wasting during the chronic phase of recovery, with implications for strength, function and general health. Although resistive exercise training effectively combats this problem, it is unknown whether sub-optimal protein intake limits the observed gains in skeletal muscle growth. Skeletal muscle adaptations may occur when resistive training (RT) is combined with nutritional therapy in the form of post- exercise protein consumption. This study would be the first to directly compare RT+protein supplementation to RT+placebo (same calories as protein supplement) in those with chronic hemiparesis caused by stroke, providing evidence-based rationale for combination therapy in the clinical care of this population.

Study Overview

• Status: Recruiting
• Conditions: Stroke
• Intervention / Treatment: Other: Placebo; Other: Protein

Detailed Description

The VA research team has played a prominent role in documenting the significant skeletal muscle atrophy that accompanies chronic hemiparesis after disabling stroke. Muscle volume is reduced by 24% in paretic vs. non-paretic legs, having significant implications for strength, function, fitness, metabolism and general health. The investigators' previous work establishes progressive, high-intensity resistive training (RT) as an effective rehabilitation strategy for older stroke survivors, producing thigh muscle hypertrophy on both the paretic and non-paretic sides. Protein supplementation can significantly augment gains in muscle mass after RT in healthy populations, but no experiments have yet been conducted in stroke. New preliminary data from the investigators' group indicates that stroke participants consume 20% less protein than the recommended daily amount for older individuals (0.80 vs. 1.0 g/kg/day) suggesting that relative gains in skeletal muscle could be significantly better in the presence of adequate protein intake. New data also indicates that leg muscle mass predicts resting metabolic rate (RMR) in stroke, implying that a combined nutrition and RT therapy aimed at maximizing muscle gains would translate into improved energy balance, a key factor in rehabilitation success. A better understanding of the true potential for aggressive RT interventions to address stroke-related atrophy and related problems for maximum benefit awaits clinical trials directly comparing RT with and without nutritional therapy. The investigators propose to conduct a 12-week randomized placebo controlled clinical trial comparing the effects of RT+ protein supplementation at 1.2 g/kg/day (RT+PRO) vs. RT+isocaloric placebo (RT+PLA) on body composition, hypertrophy, strength, functional mobility and energy expenditure in chronic stroke.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lynda C Robey; Phone Number: 5446 (410) 605-7000; Email: lynda.robey@va.gov

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD
      • Contact: Lynda C Robey; Phone Number: 5446 410-605-7000; Email: lynda.robey@va.gov
      • Principal Investigator: Alice S. Ryan, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Stroke > 3 months prior
• Completion of all regular post-stroke physical therapy
• Adequate language and neurocognitive function to participate in testing and training and to provide informed consent
• Able to walk 10 meters without human assistance

Exclusion Criteria:

• Regular structured resistive exercise (>2x/week)
• Alcohol consumption >3oz. liquor, 3 x 4oz. glasses of wine, or 3 x 12oz beers/day, by self report
• Neurological history of: a) dementia by clinical evaluation, b) severe receptive or global aphasia, which confounds testing and training, operationally defined as unable to follow 2 point commands, c) untreated major depression by clinical interview
• Medical History: a) recent hospitalization (less than 3 months prior to study entry) for severe medical disease, b) orthopedic or chronic pain condition restricting exercise, c) pulmonary or renal failure, d) active cancer, e) untreated poorly controlled hypertension measured on at least 2 occasions (greater than 190/100) f) untreated and / or poorly controlled diabetes with fasting blood glucose of greater than 170 and HbA1c greater than 10.0, g) medications: oral steroids, h) currently pregnant
• Cardiac history of: a) unstable angina, b) recent (less than 3 months prior to study entry) myocardial infarction, congestive heart failure (NYHA category II-IV); c) hemodynamically significant valvular dysfunction
• Any medical condition that, in the opinion of the Investigator, might interfere with the subject's participation in the study, poses any added risk for the subject, or confounds the assessment of the subject

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Resistive Training; Participants will drink a placebo beverage after each resistance training session.	Other: Placebo; This training is designed to target the major muscle groups of the leg. Resistance training will be completed through a combination of lower extremity machines and complemented by whole body exercises such as squatting. The lower extremity machines include leg press, leg extension, and leg curl.This group will drink a placebo beverage after each training session.
Experimental: Resistive Training + Protein; Participants will drink 30 grams of whey protein after each resistance training session.	Other: Protein; This training is designed to target the major muscle groups of the leg. Resistance training will be completed through a combination of lower extremity machines and complemented by whole body exercises such as squatting. The lower extremity machines include leg press, leg extension, and leg curl. This group will drink a beverage containing protein after each training session.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in thigh muscle area	muscle area in cm2	Measured at baseline and after the 3 month intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in muscle strength	strength	Measured at baseline and after the 3 month intervention
Change in functional mobility (6 min walk distance)	6 min walk distance	Measured at baseline and after the 3 month intervention
Change in myostatin messenger RNA (mRNA) level	myostatin mRNA (AU)	Measured at baseline and after the 3 month intervention

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Collaborators: Baltimore VA Medical Center
• Investigators: Principal Investigator: Alice S. Ryan, PhD, Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD

Publications and helpful links

General Publications

• Ryan AS, Novitskaya M, Treuth AL. Predictive Equations Overestimate Resting Metabolic Rate in Survivors of Chronic Stroke. Arch Phys Med Rehabil. 2022 Jul;103(7):1352-1359. doi: 10.1016/j.apmr.2022.01.155. Epub 2022 Feb 19.

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2015
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: January 8, 2015
• First Submitted That Met QC Criteria: January 22, 2015
• First Posted (Estimated): January 28, 2015

Study Record Updates

• Last Update Posted (Actual): July 20, 2023
• Last Update Submitted That Met QC Criteria: July 19, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Exercise; Stroke; Nutrition; Protein
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke
• Other Study ID Numbers: N1461-R; HP-00062067 (Other Identifier: Baltimore VAMC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No