Pramipexole for Opioid Withdrawal Syndrome

No longer recruiting at 1 trial location

Overseen By Benjamin W Wipper

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Massachusetts General Hospital

Must not be taking: Dopamine agonists, Dopamine antagonists

Disqualifiers: Pregnant, 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: 6

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether pramipexole can ease symptoms for individuals with Opioid Use Disorder (OUD) and Restless Legs Syndrome (RLS) during recovery. The goal is to determine if this medication can reduce withdrawal symptoms and help individuals remain committed to their treatment plans. Participants will receive either the pramipexole treatment or a placebo, a non-active substance used for comparison. Suitable candidates have already begun detoxing from opioids, experience ongoing withdrawal symptoms, and have been diagnosed with RLS. As a Phase 2/3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to significant advancements in treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have used dopaminergic medications in the last 30 days.

Is there any evidence suggesting that pramipexole is likely to be safe for humans?

Research has shown that pramipexole is generally safe for use. It is already approved for treating Parkinson's disease and Restless Legs Syndrome, indicating its safety for these conditions. Common side effects include nausea, dizziness, and drowsiness, but these are usually mild. Although no specific data exists on using pramipexole for opioid withdrawal, its FDA approval for other conditions suggests it is likely safe for short-term use. This trial will investigate its potential to alleviate symptoms of opioid withdrawal, representing a new application for the drug. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for opioid withdrawal?

Pramipexole is unique because it targets dopamine receptors, a different approach compared to most standard treatments for opioid withdrawal, which often involve medications like methadone or buprenorphine that target opioid receptors directly. Researchers are excited about pramipexole because it could offer a new way to manage withdrawal symptoms by potentially reducing cravings and improving mood without the risk of opioid dependency. This novel mechanism might provide a safer, non-addictive alternative for individuals undergoing opioid withdrawal.

What evidence suggests that pramipexole might be an effective treatment for opioid withdrawal?

Research has shown that pramipexole can alleviate symptoms of Restless Legs Syndrome, which often worsen during opioid withdrawal. In this trial, participants will receive either pramipexole or a placebo to assess its effectiveness in reducing these symptoms, potentially aiding those with Opioid Use Disorder. By easing these symptoms, pramipexole may help more individuals start and continue treatment for opioid addiction. Although pramipexole is not yet proven for this specific use, its success with Restless Legs Syndrome is promising. ^{1 2 4 6 7}

Who Is on the Research Team?

John W Winkelman, MD/PhD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with Opioid Use Disorder who've completed initial detox but still have withdrawal symptoms. They must also suffer from Restless Legs Syndrome, be willing to follow the study plan, and not have severe kidney issues, certain neurological or heart diseases, a history of RLS treatment with dopamine drugs, recent use of specific medications or substance dependencies.

Inclusion Criteria

I have opioid use disorder, completed detox, and still feel withdrawal symptoms.

My restless legs syndrome has been severe for the last three days.

You have been diagnosed with RLS through a phone interview and confirmed by a doctor.

Exclusion Criteria

You have a serious mental health condition other than opioid use disorder that needs ongoing treatment, according to the study doctors.

My kidney function is significantly reduced.

I do not have heart or neurological conditions that could make pramipexole unsafe for me.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

3 days

1 visit (in-person)

Treatment

Participants receive pramipexole or placebo for 2 weeks to assess its effects on Restless Legs Syndrome and opioid withdrawal symptoms

2 weeks

5 visits (remote via video or phone)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pramipexole

Trial Overview The study tests Pramipexole's effectiveness in reducing Restless Legs Syndrome symptoms and lingering opioid withdrawal effects to help patients stick with their Opioid Use Disorder treatment. Participants will either receive Pramipexole or a placebo without knowing which one they're getting.

How Is the Trial Designed?

Group I: Pramipexole Experimental Treatment 1 Intervention

Medication arm; 0.25 of pramipexole

Group II: Placebo Placebo Group 1 Intervention

Placebo arm; 0.25 mg of placebo

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+

Published Research Related to This Trial

Levamisole significantly increased levels of endogenous morphine and codeine in the brains and peripheral organs of morphine-addicted rats, suggesting a potential mechanism for alleviating opiate withdrawal symptoms.

The drug also altered the metabolism of key neurotransmitters like norepinephrine, dopamine, and serotonin, indicating that its effects on opiate withdrawal may be linked to changes in central nervous system function rather than direct action on opiate receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of the immunostimulant, levamisole, on opiate withdrawal and levels of endogenous opiate alkaloids and monoamine neurotransmitters in rat brain. Spector, S., Munjal, I., Schmidt, DE.[2015]

Opiate misuse is a significant issue in the UK, with many individuals suffering from withdrawal symptoms, highlighting the need for effective management strategies.

The article reviews current pharmacological treatments available for managing opiate withdrawal, emphasizing the importance of understanding clinical features to improve patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological management of opiate withdrawal. Upthegrove, RA., Naik, PC.[2019]

Nalmefene, used to treat alcohol use disorder, can cause severe opioid withdrawal symptoms if given to patients who are dependent on opioids, highlighting the importance of careful patient assessment before prescribing.

Management of opioid withdrawal in patients receiving nalmefene may require the use of opioid agonists and supportive care, emphasizing the need for a multidisciplinary approach in treating patients with co-occurring alcohol and opioid use disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of precipitated opiate withdrawal syndrome induced by nalmefene mistakenly prescribed in opiate-dependent patients: a review for clinicians. Franchitto, N., Jullian, B., Salles, J., et al.[2017]

Tramadol showed a statistically significant reduction in opioid withdrawal symptoms compared to placebo in a meta-analysis of eight clinical trials, but this effect was not consistently supported by Bayesian analysis, indicating uncertainty in its efficacy.

When compared to other treatments like buprenorphine, clonidine, and methadone, tramadol did not demonstrate a significant advantage in reducing withdrawal symptoms, suggesting it may not be a superior option for managing opioid withdrawal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tramadol in the treatment of opioid withdrawal: A meta-analysis of randomized controlled trials. Padhan, M., Maiti, R., Mohapatra, D., et al.[2023]

A study of 26 cases of loperamide misuse revealed that most patients (67%) used it to alleviate opioid withdrawal symptoms, often taking doses significantly higher than recommended, with the most common dose being 200 mg.

High doses of loperamide (>200 mg) were associated with serious cardiovascular effects, including prolonged QTc intervals and ventricular dysrhythmias, highlighting the risks of misuse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loperamide misuse to avoid opioid withdrawal and to achieve a euphoric effect: high doses and high risk. Lee, VR., Vera, A., Alexander, A., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11476544/

A novel opioid/pramipexole combination treatment for the ... Specifically, we demonstrated that the D3R agonist pramipexole enhanced morphine's analgesic effects in animal models of acute and chronic pain conditions (6).

2. mayoclinicproceedings.org mayoclinicproceedings.org/article/S0025-6196(17)30825-X/fulltext

Opioid Use in Refractory Restless Legs Syndrome Efficacy was maintained with a reduction in the International Restless Legs Syndrome Scale score from onset of the open-label phase. Drug withdrawal symptoms ...

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

Pramipexole - StatPearls - NCBI Bookshelf - NIH Apart from the FDA-approved indications, studies have shown that pramipexole has been effective in treating bipolar depression and treatment- ...

4. withpower.com withpower.com/trial/phase-2-and-3-opioid-related-disorders-9-2021-78401

Pramipexole for Opioid Withdrawal Syndrome Tramadol showed a statistically significant reduction in opioid withdrawal symptoms compared to placebo in a meta-analysis of eight clinical trials, but this ...

5. grantome.com grantome.com/grant/NIH/R21-DA052861-01

Treatment of Restless Legs Symptoms with Pramipexole to ... Thus, effective treatment of these opioid withdrawal symptoms with pramipexole has the potential to reduce the overall burden of OUD by increasing initiation, ...

6. frontiersin.org frontiersin.org/journals/pain-research/articles/10.3389/fpain.2024.1422298/full

A novel opioid/pramipexole combination treatment for the ... Our pilot clinical trial demonstrated that D3R recruitment can serve as an effective adjuvant to low-dose morphine for control of renal colic pain.

7. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/03/NCT04759703/Prot_SAP_000.pdf

partners human research committee detailed protocol PARTNERS HUMAN RESEARCH COMMITTEE DETAILED PROTOCOL. Treatment of Restless Legs Symptoms with Pramipexole to Improve the Outcomes of ...