Clinical trial NCT01052831: Naltrexone for Impulse Control Disorders in Parkinson's Disease
Official title: Randomized, Double-blind, Placebo-controlled Study of Naltrexone for Impulse Control Disorders in Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Impulse Control Disorder
Parkinson Disease
Keywords: Compulsive Gambling
Compulsive Buying
Compulsive Shopping
Compulsive Eating
Hypersexuality
Dopamine Agonists
Mirapex
Pramipexole
Requip
Ropinirole
Impulse Control Disorders
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: Michael J. Fox Foundation for Parkinson's Research
First posted: 2010-01-20
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Assessed as Very Much Improved or Much Improved Based on the Clinical Global Impression-Improvement (CGI-I) Scale
timeFrame: 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 outcomes:
measure: Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease - Rating Scale (QUIP-RS)
timeFrame: The QUIP-RS was administered at baseline and the termination visits (Visit 5, 8 weeks after baseline).
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Daniel Weintraub, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.