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| Name | Class |
|---|---|
| European Leukodystrophy Association | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| exercise | Experimental | Female carriers as well as healthy age and gender matched individuals will participate in an exercise paradigm. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| exercise training | Behavioral | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Maximal Voluntary Contraction of the Hip Flexors From Baseline to End of Training and to Post-training | 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. | Participants are assessed at baseline (visit 1, enrollment), end of training (visit 2, week 12) and post-training (visit 3, week 18). |
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Inclusion Criteria:
Exclusion Criteria:
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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| Name | Affiliation | Role |
|---|---|---|
| Kathleen M Zackowski, Ph.D. | Hugo W. Moser Research Institute at Kennedy Krieger, Inc. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Motion Analysis Lab | Baltimore | Maryland | 21205 | United States |
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| Label | URL |
|---|---|
| See Clinical Research Projects listing. | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Female Carriers | Female carriers will participate in an exercise paradigm. 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. |
| FG001 | Healthy Controls | Healthy age and gender matched individuals will participate in an exercise paradigm. 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Female Carriers | Female carriers will participate in an exercise paradigm. 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. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Maximal Voluntary Contraction of the Hip Flexors From Baseline to End of Training and to Post-training | 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. | For the follow up visit, there are fewer participants in the analysis because 5 female carriers and 1 control were unable to return for the third follow up visit due to burden to travel costs. | Posted | Mean | Standard Deviation | kg | Participants are assessed at baseline (visit 1, enrollment), end of training (visit 2, week 12) and post-training (visit 3, week 18). |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Female Carriers | Female carriers will participate in an exercise paradigm. 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. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kathleen Zackowski | Kennedy Krieger Institute | 443-923-2716 | zackowski@kennedykrieger.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 1, 2013 | Dec 7, 2017 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000326 | Adrenoleukodystrophy |
| D009043 | Motor Activity |
| ID | Term |
|---|---|
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| D015444 | Exercise |
| D055070 | Resistance Training |
| ID | Term |
|---|---|
| D009043 | Motor Activity |
| D009068 | Movement |
| D009142 | Musculoskeletal Physiological Phenomena |
| D055687 | Musculoskeletal and Neural Physiological Phenomena |
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|
| noncompliance with exercise |
|
| Healthy Controls |
Healthy age and gender matched individuals will participate in an exercise paradigm. 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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 | Healthy Controls | Healthy age and gender matched individuals will participate in an exercise paradigm. 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. |
|
|
| 0 |
| 14 |
| 0 |
| 14 |
| 0 |
| 14 |
| EG001 | Healthy Controls | Healthy age and gender matched individuals will participate in an exercise paradigm. 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. | 0 | 12 | 0 | 12 | 0 | 12 |
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| D009422 | Nervous System Diseases |
| D020279 | Hereditary Central Nervous System Demyelinating Diseases |
| D056784 | Leukoencephalopathies |
| D003711 | Demyelinating Diseases |
| D038901 | X-Linked Intellectual Disability |
| D008607 | Intellectual Disability |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D040181 | Genetic Diseases, X-Linked |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D008661 | Metabolism, Inborn Errors |
| D018901 | Peroxisomal Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D000309 | Adrenal Insufficiency |
| D000307 | Adrenal Gland Diseases |
| D004700 | Endocrine System Diseases |
| D001519 | Behavior |
| D005081 | Exercise Therapy |
| D012046 | Rehabilitation |
| D000359 | Aftercare |
| D003266 | Continuity of Patient Care |
| D005791 | Patient Care |
| D013812 | Therapeutics |
| D026741 | Physical Therapy Modalities |
| D064797 | Physical Conditioning, Human |