Pramipexole for Opioid Withdrawal Syndrome

Recruiting at1 trial location

Overseen by John W Winkelman, MD/PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: Massachusetts General Hospital

Must not be taking: Dopamine agonists, Dopamine antagonists

Disqualifiers: Pregnant, Major psychiatric disorder, others

Prior Safety Data

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests pramipexole in patients with Opioid Use Disorder to see if it can reduce Restless Legs Syndrome and withdrawal symptoms. The goal is to help these patients start and stay in treatment programs. Pramipexole is a medication that has been used to treat Parkinson's disease and restless legs syndrome (RLS).

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.

How does the drug Pramipexole differ from other treatments for opioid withdrawal?

Pramipexole is unique in treating opioid withdrawal because it primarily acts as a dopamine agonist (a substance that activates dopamine receptors in the brain), which is different from traditional treatments that often focus on opioid receptors. This mechanism may offer a novel approach to managing withdrawal symptoms by targeting the brain's dopamine system rather than the opioid system directly. ^{1 2 3 4 5}

Research Team

John W Winkelman, MD/PhD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Pramipexole (Dopamine Agonist)

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.

Participant Groups

Group I: Pramipexole Experimental Treatment 1 Intervention

Medication arm; 0.25 or 0.5 mg of pramipexole

Group II: Placebo Placebo Group 1 Intervention

Placebo arm; 0.25 or 0.5 mg of placebo

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

Findings from Research

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]

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]

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]

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]

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]

References

1. England 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. [2015]

2. England pubmed.ncbi.nlm.nih.gov

Loperamide misuse to avoid opioid withdrawal and to achieve a euphoric effect: high doses and high risk. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Management of precipitated opiate withdrawal syndrome induced by nalmefene mistakenly prescribed in opiate-dependent patients: a review for clinicians. [2017]

4. England pubmed.ncbi.nlm.nih.gov

Pharmacological management of opiate withdrawal. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tramadol in the treatment of opioid withdrawal: A meta-analysis of randomized controlled trials. [2023]