Pramipexole for Restless Legs Syndrome in ALD

Recruiting at1 trial location

Overseen by Florian Eichler, MD

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Massachusetts General Hospital

Must not be taking: Dopamine agonists, Dopamine antagonists

Disqualifiers: Pregnancy, Major psychiatric disorder, others

Prior Safety Data

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial aims to see if pramipexole can help women with ALD who have moderate to severe RLS. Pramipexole is a medication that reduces the urge to move the legs by balancing brain chemicals. The study will check if it improves symptoms and sleep quality. Pramipexole has been used effectively to treat restless legs syndrome (RLS) and improve sleep quality.

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 data supports the effectiveness of the drug pramipexole for treating restless legs syndrome?

Research shows that pramipexole, a drug used for restless legs syndrome, is effective in reducing symptoms like leg movements and sleep disturbances. Studies have demonstrated its benefits through both patient feedback and sleep studies, indicating it helps improve sleep quality and reduce discomfort. ^{1 2 3 4 5}

Is pramipexole safe for humans?

Pramipexole has been studied for its safety in treating Restless Legs Syndrome (RLS), with research indicating it is generally safe for long-term use, though it may have side effects that can affect quality of life. It is important to weigh the benefits against potential risks when considering this medication. ^{1 5 6 7 8}

How does the drug pramipexole differ from other treatments for restless legs syndrome?

Pramipexole is unique because it is a dopamine agonist (a drug that mimics dopamine, a brain chemical) with high selectivity for D2 and D3 receptors, which helps control both sensory and motor symptoms of restless legs syndrome. It is taken orally, usually 2-3 hours before bedtime, and is known for having a lower risk of augmentation (worsening of symptoms over time) compared to other treatments like levodopa. ^{2 5 9 10 11}

Research Team

Florian Eichler, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

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 between 18 and 75 years old.

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

Trial Timeline

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

Treatment Details

Interventions

• Placebo (Other)
• Pramipexole (Dopamine Agonist)

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.

Participant Groups

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 Canada, Japan for the following indications:

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+

Dr. William Curry

Massachusetts General Hospital

Chief Medical Officer

MD from Harvard Medical School

Dr. Anne Klibanski

Massachusetts General Hospital

Chief Executive Officer since 2019

MD from Harvard Medical School

European Leukodystrophy Association

Collaborator

Trials

7

Recruited

160+

Findings from Research

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 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 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]

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 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 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]

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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

The long-term effects of the dopamine agonist pramipexole in a proposed restless legs syndrome animal model. [2018]

2. Switzerland pubmed.ncbi.nlm.nih.gov

The acute effect of a low dosage of pramipexole on severe idiopathic restless legs syndrome: an open-label trial. [2018]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pramipexole in idiopathic restless legs syndrome: a polysomnographic dose-finding study--the PRELUDE study. [2018]

4. Netherlands 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. [2018]

5. Netherlands 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. [2018]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Long-term use of pramipexole in the management of restless legs syndrome. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Critical review of ropinirole and pramipexole - putative dopamine D(3)-receptor selective agonists - for the treatment of RLS. [2018]

8. Netherlands 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). [2018]

9. England pubmed.ncbi.nlm.nih.gov

Clinical experience with pramipexole in the treatment of restless legs syndrome. [2018]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and augmentation during 6 months of double-blind pramipexole for restless legs syndrome. [2018]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Pramipexole: in restless legs syndrome. [2018]