A Phase 4 interventional study of Pramipexole and Placebo in Adrenoleukodystrophy and Restless Legs Syndrome, sponsored by Massachusetts General Hospital. Active, not recruiting at 2 sites in 2 countries. Open to female participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-07-01.
Sponsored by Massachusetts General Hospital · Phase 4, Interventional, and Treatment
The investigators recently observed that up to 25% of women with X-linked adrenoleukodystrophy (ALD) have moderate to severe Restless Leg Syndrome (RLS). In this study, the investigators aim to estimate the prevalence of RLS among women with ALD and to assess whether pramipexole improves RLS symptoms as well as sleep and gait measures in women with ALD.
X-linked adrenoleukodystrophy (ALD) is a neurodegenerative disease caused by mutations in the ABCD1 peroxisomal half-transporter gene, resulting in accumulation of very long chain fatty acids (VLCFAs). As ALD is an X-linked disease, women were previously considered asymptomatic carriers. It is now known that even though adrenal insufficiency and cerebral disease occur in less than 1% of women, more than 80% eventually develop progressive spinal cord disease. Recently, the investigators observed that women are more frequently affected by movement disorders independent of the demyelinating brain disease seen in men. In a pilot study, the investigators found that up to 25% of women with ALD have moderate to severe Restless Leg Syndrome (RLS). RLS is a movement disorder characterized by a powerful urge to move the legs, usually accompanied by unpleasant dysesthesias, that is precipitated by rest, relieved by movement, and most pronounced in the evening or at night. Dopamine agonists such as pramipexole are efficacious and first-line FDA-approved treatments in low doses for primary (i.e., idiopathic) RLS and have been shown to improve both the primary symptoms of RLS (sensory discomfort, motor restlessness) as well as the associated sleep and quality of life impairments in RLS.
In the first phase of the study, the investigators will enroll 100 women with ALD at the two participating sites (Massachusetts General Hospital and University Medical Center Amsterdam). Participants will undergo structured phone interviews with both an expert in ALD and RLS to assess the presence of probable or definite RLS. Participants with probable or definite RLS will then undergo an additional phone call to determine RLS severity and assess eligibility for the second phase of the study. The objective of the first phase of the study is to determine the prevalence of RLS in women with ALD.
The second phase of the study will consist of a 4-month randomized, double-blind, placebo-controlled cross over study to assess whether pramipexole improves RLS symptoms as well as sleep and gait measures in women with ALD. The investigators will enroll 24 women with ALD and moderate to severe RLS. Participants will first be randomized 1:1 to 0.125-0.5 mg pramipexole or placebo. After the first two months, a switch-over visit will take place and include a battery of neurological assessments, walking measures, polysomnography, and questionnaires. At this visit, the crossover from pramipexole to placebo and from placebo to pramipexole will occur. The final study visit will occur 2 months after the switch-over visit and all study assessments will be repeated.
68 studies on the registry are indexed under Adrenoleukodystrophy; 19 are open to participants now.
This study's planned enrollment of 24 is below the median of 31 across 40 interventional studies indexed under Adrenoleukodystrophy.
Browse Adrenoleukodystrophy studies →Massachusetts General Hospital is the lead sponsor of 2,586 studies on the registry; 447 are open to participants now.
Of its 222 completed or terminated interventional studies of FDA-regulated products, 168 (76%) have results posted.
Counted across the registry records on this site, refreshed daily.
PHASE 1 (PREVALENCE STUDY)
Inclusion Criteria:
Exclusion Criteria:
1. Inflammatory brain demyelination
PHASE 2 (CROSS-OVER STUDY)
Inclusion Criteria:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants will be on the placebo arm for 2 months and will then cross over to the pramipexole arm for 2 months
Drug: Placebo
Participants will be on the pramipexole arm for 2 months and will then cross over to the placebo arm for 2 months
Drug: Pramipexole
Participants will be started on 0.125 mg pramipexole for the first week. If this dose is well tolerated but not effective, the dose can be increased to 0.25 mg for the following week. If this dose is well tolerated but not effective, the dose can be further increased to 0.5 mg for the remainder of the 2-month period.
Matching placebo
Change in the International Restless Legs Severity (IRLS) score
Change in IRLS score before and after pramipexole treatment. Scores range from 0 to 40, with higher scores representing more severe RLS symptoms.
Time frame: pre-intervention, week 8, week 17
Prevalence of Restless Leg Syndrome in Women with X-linked Adrenoleukodystrophy
The prevalence of RLS in women with ALD will be assessed using the Hening Telephone Diagnostic Interview (HTDI), an objective tool to diagnose RLS.
Time frame: pre-intervention
Change in the 36-Item Short Form Survey (SF-36) score
Change in SF-36 score before and after pramipexole treatment. Scores range from 0 to 100, with higher scores representing better quality of life.
Time frame: pre-intervention, week 8, week 17
Change in the Generalized Anxiety Disorder Assessment (GAD-7) score
Change in GAD-7 score before and after pramipexole treatment. Scores range from 0 to 21, with higher scores representing more severe levels of anxiety.
Time frame: pre-intervention, week 8, week 17
Change in the Patient Health Questionnaire (PHQ-9) score
Change in the PHQ-9 score before and after pramipexole treatment. Scores range from 0 to 27, with higher scores representing more severe depression.
Time frame: pre-intervention, week 8, week 17
Improvement in RLS symptoms measured by the Clinical Global Impression - Improvement (CGI-I) scale
Improvement in the patient's illness after pramipexole treatment as determined by the physician. Scores range from 1 (very much improved) to 7 (very much worse).
Time frame: week 8 and week 17
Change in the Expanded Disability Status Scale (EDSS) score
Change in EDSS score before and after pramipexole treatment. Scores range from 0 (no disability) to 10 (death).
Time frame: pre-intervention, week 8, week 17
Change in the Multiple Sclerosis Walking Scale (MSWS-12) score
Change in MSWS-12 score before and after pramipexole treatment. Scores range from 0 to 100, with higher scores representing more severe walking impairment.
Time frame: pre-intervention, week 8, week 17
Change in the Suggested Immobilization Test (SIT)
Change in the sensory and motor aspects of RLS before and after pramipexole treatment, assessed using the SIT.
Time frame: pre-intervention, week 8, week 17
Change in sleep/wake parameters measured by actigraphy
Change in sleep/wake parameters including Total Sleep time, Sleep Latency, and Wake after Sleep Onset before and after pramipexole treatment. Parameters will be objectively measured using wrist-worn actigraphy.
Time frame: pre-intervention, week 8, week 17
Change in the Utah Early Neuropathy Scale (UENS) score
Change in UENS score before and after pramipexole treatment. Scores range from 0 to 42, with higher scores representing more severe neuropathy.
Time frame: pre-intervention, week 8, week 17
Change in the Timed Up and Go (TUG) Test
Change in the amount of time it takes for the patient to get up from an armchair, walk 3 m, turn around, walk back, and sit down again before and after pramipexole treatment. Higher scores represent more severe balance impairment.
Time frame: pre-intervention, week 8, week 17
Change in the 6 Minute Walk (6MW) Test
Change in the maximum distance a patient can walk in 6 minutes before and after pramipexole treatment. Higher scores represent better walking ability.
Time frame: pre-intervention, week 8, week 17
Change in quality of sleep and leg movements per hour of sleep measured by Polysomnography
Change in quality of sleep and indices of periodic leg movements before and after pramipexole treatment. These variables will be assessed using Polysomongraphy and will be measured at the Boston site only.
Time frame: pre-intervention, week 8, week 17
Change in the 13-item Spasticity Screening Tool score
Change in the Spasticity Screening Tool before and after pramipexole treatment. Scores range from 0 to 52, with higher scores representing more severe spasticity symptoms.
Time frame: pre-intervention, week 8, week 17
Plan to share: Undecided — De-identified data will be shared between the two collaborating sites (Massachusetts General Hospital and University Medical Center of Amsterdam). We do not currently have a plan to share this data with other researchers.
No publications or documents are linked to this record.
Ran from Apr 2023 to primary completion in Jul 2025, 27 months.
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This study is active, not recruiting, as verified in Jun 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Pramipexole
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