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

• ClinicalTrials.gov Identifier: NCT01594853
• Recruitment Status: Completed
• First Posted: May 9, 2012
• Results First Posted: August 29, 2018
• Last Update Posted: August 29, 2018
• Sponsor: Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
• Collaborator: European Leukodystrophy Association
• Information provided by (Responsible Party): Kathleen Zackowski, Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
X-linked Adrenoleukodystrophy	Behavioral: exercise training	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 31 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Exercise Study of Function and Pathology for Women With X-ALD
• Study Start Date: May 2012
• Actual Primary Completion Date: October 2014
• Actual Study Completion Date: October 2014

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. 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). ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

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

Investigators

• Principal Investigator: Kathleen M Zackowski, Ph.D.; Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

  Study Documents (Full-Text)

Documents provided by Kathleen Zackowski, Hugo W. Moser Research Institute at Kennedy Krieger, Inc.:

Study Protocol and Statistical Analysis Plan  [PDF] July 1, 2013

More Information

Additional Information:

See Clinical Research Projects listing. 

• Responsible Party: Kathleen Zackowski, Principal Investigator, Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
• ClinicalTrials.gov Identifier: NCT01594853
• Other Study ID Numbers: NA_00045673
• First Posted: May 9, 2012
• Results First Posted: August 29, 2018
• Last Update Posted: August 29, 2018
• Last Verified: December 2017

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

exercise; women; training; rehabilitation; leukodystrophy

Additional relevant MeSH terms:

Adrenoleukodystrophy; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hereditary Central Nervous System Demyelinating Diseases; Leukoencephalopathies; Demyelinating Diseases; Mental Retardation, X-Linked; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Heredodegenerative Disorders, Nervous System; Metabolism, Inborn Errors; Peroxisomal Disorders; Metabolic Diseases; Adrenal Insufficiency; Adrenal Gland Diseases; Endocrine System Diseases