AdrenoleukodystrophyPhase 4NCT05003648
Treating Leg Symptoms in Women With X-linked Adrenoleukodystrophy
A Phase 4 study testing Pramipexole in people with Adrenoleukodystrophy and Restless Legs Syndrome, run by Massachusetts General Hospital at 2 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years, women only
- Conditions the study is for
- Adrenoleukodystrophy, Restless Legs Syndrome
- What is being tested?
- Pramipexole
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 1 Apr 2023to 1 Sep 2026
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- Participation in Phase 1
- Ability to provide written informed consent
- Women with ALD who have Restless Leg Syndrome (IRLS > 15)
Who cannot join
- 1. Inflammatory brain demyelination
- PHASE 2 (CROSS-OVER STUDY)
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: Treating Leg Symptoms in Women With X-linked Adrenoleukodystrophy: A Key to Improving Sleep and Gait Performance
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.
Read the detailed 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.
- Conditions
- Adrenoleukodystrophy, Restless Legs Syndrome
- Being tested
- Pramipexole, Placebo
- Medical subject headings
- Adrenoleukodystrophy, Restless Legs Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PramipexoleDrug
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.
PlaceboDrug
Matching placebo
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Pramipexole |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: pre-intervention
Secondary outcomes (13)
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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: pre-intervention, week 8, week 17
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2021
- Study start1 Apr 2023
- Primary completion16 Jul 2025
- Study completion1 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AdrenoleukodystrophyStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- European Leukodystrophy Association
- Responsible party
- Principal investigator, Florian Eichler, Massachusetts General Hospital
- Investigators
- Florian S Eichler, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05003648
- Sponsor's protocol ID
- 2021P001543
- Status last verified
- Jun 2026
- First submitted
- 15 Jul 2021
- Last updated
- 1 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treating Leg Symptoms in Women With X-linked Adrenoleukodystrophy: A Key to Improving Sleep and Gait Performance
- ClinicalTrials.gov ID
- NCT05003648
- Acronym / sponsor ID
- 2021P001543
- Conditions
- Adrenoleukodystrophy, Restless Legs Syndrome
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- European Leukodystrophy Association
- Study start
- 1 Apr 2023 (actual)
- Primary completion
- 16 Jul 2025 (actual)
- Study completion
- 1 Sep 2026 (estimated)
- First posted
- 12 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboParticipants will be on the placebo arm for 2 months and will then cross over to the pramipexole arm for 2 months |
| Pramipexole | Active comparator | Drug: PramipexoleParticipants will be on the pramipexole arm for 2 months and will then cross over to the placebo arm for 2 months |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (11 listed)
- 1. Inflammatory brain demyelination
- PHASE 2 (CROSS-OVER STUDY)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PramipexoleParticipants 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. | Drug | Pramipexole |
| PlaceboMatching placebo | Drug | Placebo |
Primary outcome
Change in the International Restless Legs Severity (IRLS) score
Time frame: pre-intervention, week 8, week 17
Change in IRLS score before and after pramipexole treatment. Scores range from 0 to 40, with higher scores representing more severe RLS symptoms.
Prevalence of Restless Leg Syndrome in Women with X-linked Adrenoleukodystrophy
Time frame: pre-intervention
The prevalence of RLS in women with ALD will be assessed using the Hening Telephone Diagnostic Interview (HTDI), an objective tool to diagnose RLS.
13 secondary outcomes
Change in the 36-Item Short Form Survey (SF-36) score
Time frame: pre-intervention, week 8, week 17
Change in the Generalized Anxiety Disorder Assessment (GAD-7) score
Time frame: pre-intervention, week 8, week 17
Change in the Patient Health Questionnaire (PHQ-9) score
Time frame: pre-intervention, week 8, week 17
Improvement in RLS symptoms measured by the Clinical Global Impression - Improvement (CGI-I) scale
Time frame: week 8 and week 17
Change in the Expanded Disability Status Scale (EDSS) score
Time frame: pre-intervention, week 8, week 17
Change in the Multiple Sclerosis Walking Scale (MSWS-12) score
Time frame: pre-intervention, week 8, week 17
Change in the Suggested Immobilization Test (SIT)
Time frame: pre-intervention, week 8, week 17
Change in sleep/wake parameters measured by actigraphy
Time frame: pre-intervention, week 8, week 17
Change in the Utah Early Neuropathy Scale (UENS) score
Time frame: pre-intervention, week 8, week 17
Change in the Timed Up and Go (TUG) Test
Time frame: pre-intervention, week 8, week 17
Change in the 6 Minute Walk (6MW) Test
Time frame: pre-intervention, week 8, week 17
Change in quality of sleep and leg movements per hour of sleep measured by Polysomnography
Time frame: pre-intervention, week 8, week 17
Change in the 13-item Spasticity Screening Tool score
Time frame: pre-intervention, week 8, week 17
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2026.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Florian S Eichler, MD principal investigator
Massachusetts General Hospital
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Pramipexole in people with Adrenoleukodystrophy and Restless Legs Syndrome, run by Massachusetts General Hospital at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 1 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the International Restless Legs Severity (IRLS) score (time frame: pre-intervention, week 8, week 17). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2026.