Exercise Study of Function and Pathology for Women With X-linked Adrenoleukodystrophy

This study has been completed.
European Leukodystrophy Association
Information provided by (Responsible Party):
Kathleen Zackowski, Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
ClinicalTrials.gov Identifier:
First received: May 7, 2012
Last updated: January 8, 2015
Last verified: January 2015
The purpose is to see how X-linked adrenoleukodystrophy (X-ALD) is associated with strength and sensation using MRI, in women with X-ALD. The investigators will also see whether exercise can improve these symptoms for women with X-ALD.

Condition Intervention
X-linked Adrenoleukodystrophy
Behavioral: exercise training

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Exercise Study of Function and Pathology for Women With X-ALD

Resource links provided by NLM:

Further study details as provided by Hugo W. Moser Research Institute at Kennedy Krieger, Inc.:

Primary Outcome Measures:
  • Change in maximal voluntary contraction of the hip flexors from baseline to end of training and to post-training [ Time Frame: Participants are assessed at baseline (visit 1, enrollment), end of training (visit 2, week 12) and post-training (visit 3, week 18). ] [ Designated as safety issue: No ]
    Here, we will assess whether the degree of a person's white matter integrity (i.e. for tracts of interest as measured from MRI) predicts their ability to benefit from exercise. Our prediction is that those individuals with preserved white matter integrity will show the greatest improvement in hip flexor strength.

Enrollment: 31
Study Start Date: May 2012
Study Completion Date: October 2014
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: exercise
Female carriers as well as healthy age and gender matched individuals will participate in an exercise paradigm.
Behavioral: exercise training
The exercise program uses a local Curves® gym to provide an individualized program of strength and cardiovascular training. The program is expected to be performed for 45 minutes 4-6 days per week.
Other Names:
  • strengthening
  • Curves

Detailed Description:
X-linked adrenoleukodystrophy (X-ALD), a [sex-linked] progressive neurodegenerative disease, is caused by a defect in the ABCD1 gene. The disease is expressed in multiple ways, but the most common adult form is adrenomyeloneuropathy (AMN), which results in slowly progressive changes in muscle tone and weakness, sensory loss, and dysfunction of the autonomic nervous system. In a previous study the investigators linked abnormalities in the [brain/spinal cord] to lower extremity weakness in men with AMN; however, there have been no studies evaluating these relationships in women carriers (i.e., women with AMN). It is unknown, in women with AMN, how the pattern of damage in the brain and spinal cord relates to disability and if these patterns predict responsiveness to treatment. The investigators hypothesize that by using magnetization transfer (MT) and diffusion tensor imaging (DTI), two magnetic resonance imaging (MRI) modalities, to track particular changes in the brain and spinal cord will predict disability and additionally, who is likely to respond best to a training regimen. The investigators expect that these more advanced imaging techniques will be more sensitive and accurate quantitative measures of clinical motor function and women with greater loss in the spinal cord compared to the brain will benefit most from training to improve disability. To test this hypothesis, women with AMN will receive MRI scans at baseline and complete measures of global walking and lower extremity impairments of vibration sensation, spasticity, and strength at three time-points: baseline, 12 weeks, and 18 weeks after baseline. The group will participate in a resistive training program for 12 weeks. MRI data will be correlated to changes over time in measures of impairment to determine their relationships. The linking of this information will not only be important for better defining disability in women with AMN but it will also help to guide physicians and rehabilitation therapists in predicting who is likely to respond to rehabilitative interventions, as well as for optimizing the effects of future pharmacological interventions.

Ages Eligible for Study:   21 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • confirmed diagnosis, X-ALD heterozygote carrier
  • no medical contraindication to participating in a strength training program
  • able to follow complex directions as determined by a score of ≤1 on a subset of questions taken from the NIH Stroke scale (Brott et al. 1989)
  • hip flexion strength: 6.6-15.8kg
  • hip extension strength: up to 18.3 kg
  • normal passive range of motion at hips/knees/ankles
  • able to walk ≥50m

Exclusion Criteria:

  • Evidence of other neurological deficit that could interfere, such as previous stroke or muscle disease
  • congestive heart failure
  • cancer
  • orthopedic conditions
  • severe pain that precludes study participation
  • seizures
  • pregnancy
  • other medical condition that precludes participation in an exercise program, e.g., unstable angina, uncontrolled diabetes, uncontrolled hypertension

Healthy controls have the same age and exclusion criteria as women with AMN except that they will not be carriers for X-ALD. They must have normal neurological function.

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01594853

United States, Maryland
Motion Analysis Lab
Baltimore, Maryland, United States, 21205
Sponsors and Collaborators
Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
European Leukodystrophy Association
Principal Investigator: Kathleen M Zackowski, Ph.D. Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
  More Information

Additional Information:
Responsible Party: Kathleen Zackowski, Principal Investigator, Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
ClinicalTrials.gov Identifier: NCT01594853     History of Changes
Other Study ID Numbers: NA_00045673 
Study First Received: May 7, 2012
Last Updated: January 8, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Hugo W. Moser Research Institute at Kennedy Krieger, Inc.:

Additional relevant MeSH terms:
Adrenal Gland Diseases
Adrenal Insufficiency
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Demyelinating Diseases
Endocrine System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Hereditary Central Nervous System Demyelinating Diseases
Heredodegenerative Disorders, Nervous System
Intellectual Disability
Mental Retardation, X-Linked
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases
Neurobehavioral Manifestations
Neurologic Manifestations
Peroxisomal Disorders

ClinicalTrials.gov processed this record on May 26, 2016