Trial of Resistance and Endurance Exercise in Amyotrophic Lateral Sclerosis (ALS)

The first questions asked by patients with a new diagnosis of Amyotrophic Lateral Sclerosis (ALS) often include: "Does exercise help slow the progression of the disease?", "Is there any harm in exercising?", or "What type of exercise (endurance or resistance) is most appropriate?" At this time, however, there is a lack of answers for people who suffer from an illness that affects their strength above all else. Yet the beneficial effects of exercise in both healthy people as well as people with other diseases have been extensively studied and resulted in recommendations about the types of exercise that are beneficial. In this study the investigators will ask participants with ALS to exercise in one of three ways: weightlifting (resistance exercise), stationary bicycling (endurance exercise), and range of motion exercise (the current "standard of care" for ALS patients). The investigators will use several different types of tests to determine whether one type of exercise is tolerated better and is safer than another. The investigators will also collect information about how the body responds to exercise in ALS. This study will help in the development of a larger national study to understand how exercise can be combined with other treatments to potentially improve strength and alter the course of the disease.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Other: Resistance Exercise; Other: Endurance Exercise; Other: Stretching/Range-of-Motion

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • Massachusetts
    • Charlestown, Massachusetts, United States, 02129
      • Massachusetts General Hospital
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Carolinas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Participants with familial or sporadic ALS diagnosed as possible, laboratory-supported probable, probable, or definite according to the WFN El Escorial criteria
2. Participants who are ages 18-80, inclusive.
3. Slow Vital Capacity (SVC) must be equal to or greater than 70% of predicted value
4. ALSFRS-R score >30.
5. Patients who are currently on any medications must be on a stable dose for the past 30 days.
6. Participants must provide informed consent prior to completion of any study procedures.

Exclusion Criteria:

1. Participants who are already performing >30 min. of endurance exercise/day for ≥ 3x/week (Borg scale-- "hard" or "somewhat hard") within 30 days of screening.
2. Participants who are already performing resistance exercise ≥ 3x/week within 30 days of screening.

3. Neurologic

   • Participants with history of ALS symptoms over 5 years duration
   • Inability to obtain consent (psychiatric or dementing illness)
   • History of neuromuscular dysfunction not related to ALS

4. Cardiac

   • Patents with clinically significant ECG abnormalities
   • Uncontrolled hypertension (SBP>160 or DBP>110)
   • Recent history of angina (within the last 2 years)
   • Recent history of abnormal stress test (within the last 2 years)
   • Symptomatic severe aortic stenosis
   • Active endocarditis
   • Symptomatic heart failure

5. Respiratory

   • Subjects with a history of respiratory dysfunction not related to ALS (i.e. COPD)

6. General

   • Subjects with chronic infectious disease including HIV, hepatitis B or C.
   • History of substance abuse within the past year
   • Patients who have a history of poor compliance to medical regimens or study requirements.
   • Uncontrolled diabetes
   • Recent embolism (within the last 6 months)
   • Severe orthopedic conditions that would prohibit exercise

7. Pregnancy

   • Female subjects who are pregnant or planning to become pregnant.
   • Female subjects of childbearing potential who are not practicing contraception.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Resistance Exercise; Resistance will be administered using a series of adjustable cuff weights for the upper limbs and hip flexion. Knee flexion and extension will be administered with a weight bench using a leg exercise attachment and free weights.	Other: Resistance Exercise; Resistance will be administered using a series of adjustable cuff weights for the upper limbs and hip flexion. Knee flexion and extension will be administered with a weight bench using a leg exercise attachment and free weights.
Active Comparator: Endurance Exercise; Endurance will be administered using a minicycle. It can be used from a sitting position (chair or wheelchair) for lower limb exercise and then placed on a tabletop for upper limb use.	Other: Endurance Exercise; Endurance will be administered using a minicycle. It can be used from a sitting position (chair or wheelchair) for lower limb exercise and then placed on a tabletop for upper limb use.
Active Comparator: Stretching/Range-of-Motion Exercise; In ALS, stretching and range of motion are routinely recommended for the prevention of "frozen shoulder syndrome" and contractures resulting from weakness. The problem is compounded in ALS where upper motor neuron dysfunction may result in spasticity and incapacitating contractures with pain. Therefore, maintaining an aggressive program for stretching and range of motion exercise is widely accepted as a "standard of care" for ALS management.	Other: Stretching/Range-of-Motion; Stretching and range of motion exercise is widely accepted as a "standard of care" for ALS management.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resistance Exercise Tolerability	Evaluate the tolerability of RESISTANCE exercise in ALS subjects as measured by their ability to complete a 6 month study of a resistance exercise regimen.	6 months
Endurance Exercise Tolerability	Evaluate the tolerability of ENDURANCE exercise in ALS subjects as measured by their ability to complete a 6 month study of an endurance exercise regimen.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vital Capacity	Evaluate the effect of resistance and endurance exercise on slow vital capacity (SVC)	6 months
ALS Functional Rating Scores	Evaluate the effect of resistance and endurance exercise on patients scores of the ALS Functional rating scale-revised (ALSFRS-R)	6 months
Muscle Strength	Evaluate the effect of resistance and endurance exercise on measures of muscle strength	6 months
Spasticity	Evaluate the effect of resistance and endurance exercise on spasticity	6 months
Fatigue	Evaluate the effect of resistance and endurance exercise on fatigue	6 months
Quality of Life	Evaluate the effect of resistance and endurance exercise on patient quality of life	6 months

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: ALS Association
• Investigators: Principal Investigator: Nicholas M Maragakis, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: January 24, 2012
• First Submitted That Met QC Criteria: January 26, 2012
• First Posted (Estimate): January 31, 2012

Study Record Updates

• Last Update Posted (Estimate): April 19, 2016
• Last Update Submitted That Met QC Criteria: April 18, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Exercise; ALS; Resistance; Endurance
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: NA_00022650