Effect of Functional Exercise in Patients With Spinal Bulbar Muscular Atrophy
Condition: Motor Neuron Disease
MeSH terms: Muscular Atrophy; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Bulbo-Spinal Atrophy, X-Linked; Atrophy
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Background:

      -Spinal and bulbar muscular atrophy (SBMA) is an inherited disorder that affects men. People
      with SBMA often have weakness throughout the body, including the muscles they use for
      swallowing, breathing, and speaking. We do not know if exercise helps or harms people with
      SBMA.

      Objective:

      -To see if a 12-week program of either functional exercise or stretching exercises will
      improve strength, function, or quality of life in people with SBMA

      Eligibility:

        -  Participants will be men 18 years of age or older who have genetic confirmation of SBMA.

        -  They must be able to walk at least 50 feet with or without an assistive device such as a
           cane or a walker and stand for 10 minutes without using an assistive device.

        -  They must have access to a computer with an Internet connection.

      Design:

        -  At the first visit to NIH (2 days), participants will have a medical history taken and
           undergo a physical exam. They will also have blood tests and an EKG, and complete
           questionnaires about mood, health, and exercise. Tests of muscle strength, balance, and
           endurance will also be done.

        -  Participants who qualify for the study will receive instruction about either
           strengthening or stretching exercises. They will do these exercises at home one to three
           times a week for 12 weeks.

        -  They will wear a small activity monitor while they exercise and record their exercise in
           a diary.

        -  At the end of 12 weeks, participants will return to the NIH for 2 days. They will
           undergo the same tests as they had on the first visit.

        -  Participants will receive follow-up phone calls and e-mails during the study and for 4
           weeks after the last visit....
    

Detailed description: 
      Objective: Spinal and bulbar muscular atrophy (SBMA), or Kennedy s disease, is a slowly
      progressive, X-linked motor neuron disease for which there is currently no treatment. It is
      caused by a mutation in the androgen receptor that results in a polyglutamine repeat
      expansion. The role of exercise in motor neuron disease research is debated. Although SBMA is
      believed to be primarily a neuronopathy, the potential effect of aberrant androgen receptor
      activity on muscle leads exercise to be of uncertain utility in this population. Our
      objective is to examine the safety and efficacy of exercise regimens in Kennedy s disease.

      Study Population: We aim to enroll 80 men with genetically confirmed Kennedy s disease.

      Design: This will be a randomized, evaluator blinded, trial with 25 subjects in each exercise
      arm. Following informed consent, the subjects will undergo an initial medical and physical
      evaluations followed by a series of neurological tests and blood work over a two-day
      outpatient visit at the NIH. The subjects will provide blood work for analysis of hormonal
      levels and assessment of any potential muscle damage. On the second day of their visit, the
      subjects will be randomized and taught a series of either functional or stretching exercises
      that they will engage in as part of the study and control arms, respectively. Following the
      baseline visit to NIH, the subjects will be monitored throughout the study with telephone
      contacts and other measures including video recording to monitor their progress and
      compliance. The subjects will return to the NIH at the end of a 12 week period at which time
      the physical and laboratory testing will be repeated. After the 12 week exercise period there
      will be a four week period where we will follow-up with the participants by telephone and
      e-mail. At the end of the trial all of the subjects will be informed of the study results and
      given the opportunity to learn the exercises if they are found to be beneficial.

      Outcome Measures: The primary outcome measure used will be the Adult Myopathy Assessment Tool
      (AMAT). Secondary outcome measures will involve quantitative muscle analysis (QMA), the Timed
      Up and Go (TUG) test, a quality of life measure (SF-36v2TM), adverse event questionnaires, a
      Computerized Dynamic Posturography (CDP) assessment of balance, accelerometer measurements of
      exercise effort, and progressive height sit-to-stand testing. Several exploratory biomarkers
      that may be affected by exercise will be evaluated, including insulin-like growth factor-1
      (IGF-1), insulin-like growth factor binding protein 3, testosterone, growth hormone, and
      creatine kinase. Beck Depression Inventory (BDI) testing will also be used to determine if
      the subjects mood is affected by exercise. Qualitative sub-study questions, international
      index of erectile function, Block brief food questionnaire, Aggression Questionnaire,
      Activities-specific Balance Confidence (ABC) scale, Fatigue Symptom Inventory, and physical
      activity survey measures will also be employed.
    

Intervention name(s): A functional exercise program; A stretching exercise program
Intervention type(s): Behavioral; Behavioral
Allocation: Randomized
Intervention model: Parallel Assignment
Primary purpose: Treatment
Keywords: Exercise; Spinal Bulbar Muscular Atrophy; Spinal and Bulbar Muscular Atrophy; SBMA; Motor Neuron Disease