Pramipexole for Restless Legs Syndrome in ALD

Recruiting at 1 trial location

Overseen By Riya Saxena

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: Massachusetts General Hospital

Must not be taking: Dopamine agonists, Dopamine antagonists

Disqualifiers: Pregnancy, Major psychiatric disorder, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether the drug pramipexole can help women with Restless Leg Syndrome (RLS) who also have X-linked adrenoleukodystrophy (ALD), a genetic disorder. Researchers aim to determine if pramipexole can improve RLS symptoms, sleep, and walking. Participants will first receive either pramipexole or a placebo (a pill without active medicine) for two months and then switch to the other treatment. Women with ALD who experience moderate to severe RLS might be suitable candidates for this study. As a Phase 4 trial, pramipexole is already FDA-approved and proven effective, and this research seeks to understand how it benefits more patients.

Will I have to stop taking my current medications?

The trial requires that you have not used dopaminergic medications (drugs that affect dopamine levels) in the last 30 days. If you are currently taking these, you would need to stop for at least 30 days before participating.

What is the safety track record for pramipexole?

Research shows that pramipexole is well-studied for treating Restless Legs Syndrome (RLS) and is generally well-tolerated. About 7% of patients with RLS who took pramipexole stopped due to side effects, compared to 5% of those taking a placebo (a pill with no active ingredients). This suggests that pramipexole's side effects are similar to those of a placebo.

Pramipexole has already received approval for treating RLS, indicating that its safety has been thoroughly evaluated. While some individuals may experience side effects, the drug is considered safe for the general public to use for RLS. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Pramipexole is unique because it offers a different approach to managing Restless Legs Syndrome (RLS) in the context of ALD, compared to the standard dopamine agonists and other treatments like gabapentin or opioids. Pramipexole specifically targets dopamine receptors, potentially providing more targeted symptom relief with fewer side effects. Researchers are excited about its potential to offer a more precise treatment option that directly addresses the underlying neurological pathways involved in RLS. This could mean more effective relief for patients with fewer complications, giving it an edge over current therapies.

What is the effectiveness track record for pramipexole in treating Restless Legs Syndrome?

Research has shown that pramipexole, which participants in this trial may receive, effectively treats Restless Legs Syndrome (RLS). In a study with 107 patients, it significantly reduced leg movements in those with RLS. Another analysis found that pramipexole improved symptoms in people with moderate to severe RLS. This treatment works by balancing certain chemicals in the brain, reducing symptoms. Overall, strong evidence supports pramipexole's effectiveness in managing RLS. ^{1 6 7 8 9}

Who Is on the Research Team?

Florian Eichler, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for women aged 18-75 with X-linked adrenoleukodystrophy (ALD) who suffer from moderate to severe Restless Leg Syndrome (RLS). Participants must have a confirmed diagnosis of ALD, be able to consent, and comply with study procedures. Exclusions include recent alcohol or drug dependence, pregnancy, prior RLS treatment with dopamine agonists, certain medical conditions like renal disease or inflammatory brain issues, and use of dopaminergic drugs within the last month.

Inclusion Criteria

Ability to provide written informed consent

A willingness and ability to comply with study procedures

I am a woman with ALD and have severe restless leg syndrome.

Exclusion Criteria

You have been dependent on methamphetamine or benzodiazepines in the last 30 days.

Pregnant. Research staff perform pregnancy tests upon visit to center

Medical instability considered to interfere with study procedures

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Structured phone interviews

Prevalence Assessment

Determine the prevalence of RLS in women with ALD through structured phone interviews

2-4 weeks

Phone interviews

Treatment

4-month randomized, double-blind, placebo-controlled cross over study to assess pramipexole's effect on RLS symptoms

16 weeks

Multiple visits including switch-over and final assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Pramipexole

Trial Overview The study aims to determine how common RLS is in women with ALD and if pramipexole can improve their symptoms. It will also look at sleep quality and walking ability. Women participating will either receive pramipexole or a placebo without knowing which one they are taking.

How Is the Trial Designed?

Group I: Pramipexole Active Control 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

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

Pramipexole is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Mirapex for:

• Parkinson's disease
• Restless Legs Syndrome

Approved in European Union as Mirapexin for:

• Parkinson's disease
• Restless Legs Syndrome

Approved in Canada as Sifrol for:

• Parkinson's disease
• Restless Legs Syndrome

Approved in Japan as Glepark for:

• Parkinson's disease
• Restless Legs Syndrome

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

European Leukodystrophy Association

Collaborator

Trials

7

Recruited

160+

Published Research Related to This Trial

Pramipexole, a dopamine agonist recently approved for treating restless legs syndrome (RLS), significantly reduced periodic limb movements and improved RLS symptoms in adults, with a median dosage of 0.35 mg/day showing a greater reduction in the International RLS Study Group rating scale compared to placebo.

In a controlled study, patients who continued on pramipexole after 6 months experienced significantly less worsening of symptoms compared to those switched to placebo, indicating its effectiveness in maintaining symptom control, and it was generally well tolerated with mostly mild side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pramipexole: in restless legs syndrome. McCormack, PL., Siddiqui, MA.[2018]

Pramipexole is an effective treatment for idiopathic restless legs syndrome, with a single oral dose of 0.125 to 0.750 mg taken before bedtime effectively controlling symptoms.

The medication is generally safe and well tolerated, with a lower incidence of augmentation compared to levodopa, making it a favorable option for managing restless legs syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with pramipexole in the treatment of restless legs syndrome. Merlino, G., Serafini, A., Robiony, F., et al.[2018]

Chronic treatment with pramipexole (PPX) for 28 to 84 days significantly reduced excessive locomotor activity in a mouse model of restless legs syndrome (RLS), indicating its efficacy in alleviating RLS-like symptoms.

PPX treatment also showed a partial recovery of spinal iron deficiency in the mice, suggesting a potential mechanism of action that may involve improving iron levels alongside its effects on dopamine receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The long-term effects of the dopamine agonist pramipexole in a proposed restless legs syndrome animal model. Luo, F., Li, C., Ondo, WG., et al.[2018]

In a study involving 10 patients with severe idiopathic restless legs syndrome (RLS), a low dose of pramipexole (0.125 mg) significantly improved both sensory symptoms and motor signs of RLS after just one administration.

The acute administration of pramipexole also positively affected various parameters of sleep quality, indicating its potential for immediate therapeutic benefits in RLS management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The acute effect of a low dosage of pramipexole on severe idiopathic restless legs syndrome: an open-label trial. Merlino, G., Dolso, P., Canesin, R., et al.[2018]

In a 26-week study involving 107 adults with moderate to severe Restless Legs Syndrome (RLS), pramipexole significantly reduced RLS symptoms, with an average score reduction of 73.5% and an 81.3% responder rate.

Pramipexole was well tolerated, showing improvements in sleep quality and overall health without increasing daytime sleepiness, although some patients reported common side effects like headache and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label study of the long-term efficacy and safety of pramipexole in patients with Restless Legs Syndrome (extension of the PRELUDE study). Partinen, M., Hirvonen, K., Jama, L., et al.[2018]

In a 3-week study involving 107 patients, pramipexole significantly reduced periodic limb movements (PLM) in patients with restless legs syndrome (RLS), with reductions ranging from -26.55 to -52.70 PLM per hour compared to only -3.00 for placebo.

Pramipexole was well tolerated, showing no dose-dependent increase in adverse events, and improved subjective ratings of RLS severity and sleep disturbance, indicating its efficacy and safety as a treatment for RLS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A dose-ranging study of pramipexole for the symptomatic treatment of restless legs syndrome: polysomnographic evaluation of periodic leg movements and sleep disturbance. Jama, L., Hirvonen, K., Partinen, M., et al.[2018]

In a study of 109 patients with moderate to severe restless legs syndrome (RLS), pramipexole significantly reduced periodic limb movements and improved patient-reported symptoms compared to placebo, with the most notable effects seen at the 0.50 mg dose.

Pramipexole was well tolerated, showing no significant side effects like somnolence, and resulted in a higher percentage of patients reporting substantial improvement in their condition compared to those receiving placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pramipexole in idiopathic restless legs syndrome: a polysomnographic dose-finding study--the PRELUDE study. Partinen, M., Hirvonen, K., Jama, L., et al.[2018]

In a long-term study of 50 patients using pramipexole for restless legs syndrome (RLS) over an average of 8 years, the effectiveness of the medication decreased over time, with only 40% reporting it as completely effective by the end of the study.

A significant number of patients (42%) experienced augmentation of symptoms and 74% reported side effects, including daytime sleepiness and impulse control disorders, indicating a need for alternative non-dopaminergic treatments for RLS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term use of pramipexole in the management of restless legs syndrome. Lipford, MC., Silber, MH.[2018]

Ropinirole and pramipexole are FDA-approved medications for treating restless legs syndrome (RLS), a condition that may be more common than previously recognized, highlighting the need for better awareness and understanding of RLS.

While these drugs target dopamine D(3) receptors and show potential benefits, they also have adverse effects that can impact quality of life, necessitating careful consideration of their benefit-to-risk ratio in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Critical review of ropinirole and pramipexole - putative dopamine D(3)-receptor selective agonists - for the treatment of RLS. Varga, LI., Ako-Agugua, N., Colasante, J., et al.[2018]

In a 26-week study involving 331 patients with restless legs syndrome, pramipexole significantly improved symptoms compared to placebo, with a greater reduction in the International RLS Study Group Rating Scale (IRLS) score (-13.7 vs. -11.1) and a higher responder rate (58.6% vs. 42.8%).

While pramipexole was effective and generally well tolerated, there was a 9.2% incidence of confirmed augmentation in patients taking the drug, suggesting that longer-term studies are needed to fully understand its effects and risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and augmentation during 6 months of double-blind pramipexole for restless legs syndrome. Högl, B., Garcia-Borreguero, D., Trenkwalder, C., et al.[2018]

In a 6-week study involving Japanese patients with moderate to severe restless legs syndrome (RLS), pramipexole significantly reduced the periodic limb movements in bed index (PLMI) compared to placebo, indicating its efficacy in managing RLS symptoms.

Patients taking pramipexole also reported significant improvements in overall RLS severity and sleep quality, as measured by various scales, highlighting its effectiveness in enhancing both objective and subjective measures of the disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pramipexole in Japanese patients with primary restless legs syndrome: A polysomnographic randomized, double-blind, placebo-controlled study. Inoue, Y., Hirata, K., Kuroda, K., et al.[2018]

Citations

1. withpower.com withpower.com/trial/phase-4-restless-legs-syndrome-8-2021-0b421

Pramipexole for Restless Legs Syndrome in ALD In a 3-week study involving 107 patients, pramipexole significantly reduced periodic limb movements (PLM) in patients with restless legs syndrome (RLS), with ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4972503/

Efficacy of pramipexole for the treatment of primary restless ... This meta-analysis study indicated that pramipexole could effectively improve the symptoms of primary moderate to severe RLS patients, although the quality of ...

3. go.drugbank.com go.drugbank.com/drugs/DB00413

Pramipexole: Uses, Interactions, Mechanism of Action Pramipexole is a non-ergot dopamine agonist used to treat the signs and symptoms of idiopathic Parkinson's disease and Restless Legs Syndrome (RLS).

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3321653/

Pramipexole in restless legs syndrome: an evidence-based ... There is clear evidence that pramipexole is effective in reducing the leg movements associated with RLS, the major outcome measure of the disease.

5. mayoclinic.org mayoclinic.org/drugs-supplements/pramipexole-oral-route/description/drg-20065603

Pramipexole (oral route) - Side effects & dosage Pramipexole is also used to treat Restless Legs Syndrome (RLS). RLS is a neurologic disorder that affects sensation and movement in the legs ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2008/020667s014s017s018lbl.pdf

Mirapex® - accessdata.fda.gov The pharmacokinetics of pramipexole were comparable between early and advanced Parkinson's disease patients. Restless Legs Syndrome Patients. A cross-study ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK557539/

Pramipexole - StatPearls - NCBI Bookshelf - NIH Pramipexole is a medication used in the management and treatment of Parkinsonism and restless leg syndrome. It is in the anti-parkinsonian class of drugs.

8. drugs.com drugs.com/mtm/pramipexole.html

Pramipexole Uses, Side Effects & Warnings Pramipexole is also used to treat restless legs syndrome (RLS). Only ... -Extended-release tablets are not indicated for Restless Legs Syndrome.

9. aafp.org aafp.org/pubs/afp/issues/2007/0415/p1239.html

Pramipexole (Mirapex) for Restless Legs Syndrome Approximately 7 percent of patients with RLS receiving pramipexole discontinued treatment because of adverse effects compared with 5 percent of ...