Naltrexone for Impulse Control Disorders in Parkinson's Disease

Randomized, Double-blind, Placebo-controlled Study of Naltrexone for Impulse Control Disorders in Parkinson's Disease

This study will evaluate the effectiveness of naltrexone in reducing ICD symptoms in Parkinson's disease patients taking a dopamine agonist.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease; Impulse Control Disorder
• Intervention / Treatment: Drug: Naltrexone; Drug: Placebo

Detailed Description

Impulse control disorders (ICDs), including compulsive gambling, sexual behavior, buying, and eating, are increasingly recognized as a significant clinical problem in Parkinson's disease (PD), occurring in up to 15% of patients. Dopamine agonist (DA) treatment is thought to be the primary risk factor for the development of ICDs in PD. ICDs often lead to significant impairments in psychosocial functioning, interpersonal relationships, and quality of life. The management of ICDs in the context of PD can be complex. Patients may be reluctant to discontinue DA treatment due to the motor benefits derived from treatment, so patients often have chronic symptoms. Thus, additional treatment approaches are needed.

A medication shown to be efficacious for the treatment of ICDs with minimal impact on parkinsonism would allow many ICD patients to continue on full-dose DA treatment. Naltrexone, a long-acting opioid receptor antagonist, helps in the treatment of alcohol and opioid dependence. In addition, placebo-controlled studies have demonstrated that it helps in the treatment of pathological gambling in the general population. Opioids regulate dopamine pathways in areas of the brain linked with impulse control disorders, and opioid antagonists block opioid receptors in these regions. In this study, 48 PD patients with an ICD will be treated either with naltrexone (50-100 mg/day) or placebo for a period of 8 weeks. The study will assess if naltrexone improves ICD symptoms in PD and is well tolerated. To our knowledge, the proposed study is the first controlled trial of an agent to treat ICDs in PD.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Diagnosis of possible or probable idiopathic Parkinson's disease (PD).
2. Ages 18-85 years.
3. Diagnosis of compulsive gambling, buying, sex behavior, or eating of >2 months duration.
4. Impulse control disorder (ICD) behaviors that began after PD onset and in context of dopamine agonist (DA) treatment.
5. Current stable DA use. Participants must be on a DA for 6 months and on a stable dose (no changes) for 1 month prior to enrolling the in the study.
6. Subjects are capable of giving informed consent, supported by not having significant cognitive impairment based on Montreal Cognitive Assessment score ≥24.
7. Willingness to maintain existing PD pharmacotherapy regimen for the duration of the study.

Exclusion Criteria

1. Active suicide ideation.
2. Anticipated need to initiate antidepressant therapy during the course of the study (must be on a dose in the therapeutic range for at least 2 months. If patient does end up needing to start antidepressant or change antidepressant dose during the course of the study, he/she will be allowed to continue study participation).
3. ICD behaviors so severe that modification of DA treatment is clinically warranted, as judged by PI.
4. Deep brain stimulation surgery in the past year.
5. Evidence for significant liver disease by chart review or patient history (e.g., cirrhosis, chronic hepatitis, liver transplant, or liver cancer).
6. Meeting diagnostic criteria for alcohol or opiate dependence.
7. Meeting diagnostic criteria for Dopamine Dysregulation Syndrome.
8. Use of opioids for pain management.
9. Females that are pregnant, planning to become pregnant, or are breastfeeding will not be included in the study. Females of child bearing potential will need to verify that they are not pregnant by a negative urine pregnancy test.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Naltrexone; For the first four weeks of the study, participants were administered naltrexone at 50mg per day. Participants not in response at week 4 were increased to 100mg per day for the remaining four weeks of the study.	Drug: Naltrexone; 50-100 mg qd for 8 weeks; Other Names: Revia, Vivitrol
Placebo Comparator: Placebo; Participants received the placebo treatment which looked identical to active study medication.	Drug: Placebo; 50-100 mg qd for 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Assessed as Very Much Improved or Much Improved Based on the Clinical Global Impression-Improvement (CGI-I) Scale	The Clinical Global Impression-Improvement scale rates total improvement on a 7 point scale: = Very much improved; = Much improved; = Minimally improved; = No change; = Minimally worse; = Much worse; = Very much worse A participant scoring a 1 or 2 is considered a responder on the CGI scale. For the change in response status over time, a generalized estimating equation (GEE) model was used.	The CGI-I was administered at Visit 2 (week 2, two weeks after baseline) and Visit 5 (week 8, termination visit 8 weeks after baseline).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease - Rating Scale (QUIP-RS)	The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) was developed for use in clinical trials and added as a secondary outcome measure for assessment of change in severity of ICD symptoms, to be completed at baseline and end of study only. For the QUIP-RS, scores for each compulsive behavior range from 0 to 16, with a higher score indicating greater severity (frequency) of symptoms. Given that ICD symptoms are frequently comorbid in patients with PD, total QUIP-RS ICD scores (range from 0 to 64) were used to compare overall severity of ICD symptoms. Please note that this measure is reporting a change from baseline.	The QUIP-RS was administered at baseline and the termination visits (Visit 5, 8 weeks after baseline).

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: Michael J. Fox Foundation for Parkinson's Research

Publications and helpful links

General Publications

• Papay K, Xie SX, Stern M, Hurtig H, Siderowf A, Duda JE, Minger J, Weintraub D. Naltrexone for impulse control disorders in Parkinson disease: a placebo-controlled study. Neurology. 2014 Aug 26;83(9):826-33. doi: 10.1212/WNL.0000000000000729. Epub 2014 Jul 18.

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: January 15, 2010
• First Submitted That Met QC Criteria: January 15, 2010
• First Posted (Estimate): January 20, 2010

Study Record Updates

• Last Update Posted (Estimate): August 6, 2015
• Last Update Submitted That Met QC Criteria: July 13, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Pramipexole; Dopamine Agonists; Ropinirole; Requip; Compulsive Gambling; Compulsive Buying; Compulsive Shopping; Compulsive Eating; Hypersexuality; Mirapex; Impulse Control Disorders
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Disease; Parkinson Disease; Disruptive, Impulse Control, and Conduct Disorders; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Alcohol Deterrents; Naltrexone
• Other Study ID Numbers: 810624