Treating Leg Symptoms in Women With X-linked Adrenoleukodystrophy

NCT05003648 | Active Not Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 2021P001543
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 2

Brief 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.

Conditions

Restless Legs Syndrome; Adrenoleukodystrophy

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  pre-intervention

Secondary Outcomes (13)

• Change in the 36-Item Short Form Survey (SF-36) score

  pre-intervention, week 8, week 17

• Change in the Generalized Anxiety Disorder Assessment (GAD-7) score

  pre-intervention, week 8, week 17

• Change in the Patient Health Questionnaire (PHQ-9) score

  pre-intervention, week 8, week 17

• Improvement in RLS symptoms measured by the Clinical Global Impression - Improvement (CGI-I) scale

  week 8 and week 17

• Change in the Expanded Disability Status Scale (EDSS) score

  pre-intervention, week 8, week 17

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Participants will be on the placebo arm for 2 months and will then cross over to the pramipexole arm for 2 months

Drug: Placebo

Pramipexole

ACTIVE COMPARATOR

Participants will be on the pramipexole arm for 2 months and will then cross over to the placebo arm for 2 months

Drug: Pramipexole

Interventions

Pramipexole DRUG

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.

Pramipexole

Placebo DRUG

Matching placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• \. Inflammatory brain demyelination
• PHASE 2 (CROSS-OVER STUDY)
• Participation in Phase 1
• Ability to provide written informed consent
• Women with ALD who have Restless Leg Syndrome (IRLS \> 15)
• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• European Leukodystrophy Association: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University Medical Center of Amsterdam

Amsterdam, Netherlands

Location

MeSH Terms

Conditions

Adrenoleukodystrophy; Restless Legs Syndrome

Interventions

Pramipexole

Condition Hierarchy (Ancestors)

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; X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System; Metabolism, Inborn Errors; Peroxisomal Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Adrenal Insufficiency; Adrenal Gland Diseases; Endocrine System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Parasomnias; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzothiazoles; Thiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Florian S Eichler, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Neurology

Study Record Dates

• First Submitted: July 15, 2021
• First Posted: August 12, 2021
• Study Start: April 1, 2023
• Primary Completion: July 15, 2025
• Study Completion: May 1, 2026
• Last Updated: March 2, 2026

Record last verified: 2026-02

Locations

US (1); NL (1)