Multiple Sclerosis Clinical Trial

Treating Leg Symptoms in Women With X-linked Adrenoleukodystrophy

Summary

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.

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Full Description

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.

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Eligibility Criteria

PHASE 1 (PREVALENCE STUDY)

Inclusion Criteria:

Women of any ethnic origin.
Ability to provide verbal consent
A willingness and ability to comply with study procedures.
Age 18-75 years
Metabolically or genetically confirmed diagnosis of ALD

Exclusion Criteria:

1. Inflammatory brain demyelination

PHASE 2 (CROSS-OVER STUDY)

Inclusion Criteria:

Participation in Phase 1
Ability to provide written informed consent
Women with ALD who have Restless Leg Syndrome (IRLS > 15)

Exclusion Criteria:

Pregnant. Research staff perform pregnancy tests upon visit to center.
Participants with active or unstable major psychiatric disorder other than ALD, who, in the investigators' judgement, require further treatment
Use of dopaminergic agonists or antagonists within the last 30 days
Alcohol use disorder within the last 30 days
History of being treated for restless legs syndrome, specifically with dopamine agonist medications
Methamphetamine or benzodiazepine dependence in the last 30 days
Neurological disorder or cardiovascular disease raising safety concerns about use of pramipexole and/or judged to interfere with ability to assess efficacy of the treatment
Medical instability considered to interfere with study procedures
Renal disease judged to interfere with drug metabolism and excretion

Study is for people with:

Multiple Sclerosis

Phase:

Phase 4

Estimated Enrollment:

24

Study ID:

NCT05003648

Recruitment Status:

Recruiting

Sponsor:

Massachusetts General Hospital

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There is 1 Location for this study

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Massachusetts General Hospital
Boston Massachusetts, 02114, United States More Info
Riya Saxena
Contact
603-674-6743
[email protected]
Florian S Eichler, MD
Principal Investigator
University Medical Center of Amsterdam
Amsterdam , , Netherlands More Info
Marc Engelen, MD, PhD
Contact
+31-20-5667508
[email protected]
Marc Engelen, MD, PhD
Principal Investigator

How clear is this clinincal trial information?

Study is for people with:

Multiple Sclerosis

Phase:

Phase 4

Estimated Enrollment:

24

Study ID:

NCT05003648

Recruitment Status:

Recruiting

Sponsor:


Massachusetts General Hospital

How clear is this clinincal trial information?

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