Evaluation of Nalmefene in Impulse Control Disorders in Parkinson's Disease: A Prospective Open Label Study (Nalmefene TCI)

Impulse control disorders (ICDs) (such as pathological gambling, hypersexuality, compulsive shopping …) are an increasingly recognized psychiatric complications in Parkinson's disease (PD). Therapeutic management of these disorders is important since they have an impact on patient quality of life. Dopamine agonists play a key role in the emergence of ICD.

Animal models and imaging underline the implication of opioid system in the genesis of ICD.

An opioid antagonist, the naltrexone, has been studied to treat ICDs in PD. Papay and al 2014 have found that patients treated by naltrexone showed an interesting decrease of their ICDs measured by the QUIP RScale. Nevertheless, naltrexone has shown adverse effects such as increasing hepatic liver enzymes. Nalmefene has no known hepatic adverse effects. Nalmefene is an opioid antagonist that has an antagonist action on μ and δ receptors, but also an agonist action on κ receptor. Grant and al 2006 has shown significant reduction of the severity of pathological gambling in patients treated with nalmefene.

The primary purpose is to evaluate the efficacy and the safety of nalmefene in the treatment of ICDs in PD.

Study Overview

• Status: Unknown
• Conditions: Parkinson Disease; Impulse Control Disorders
• Intervention / Treatment: Drug: Nalmefene

Detailed Description

In this open study, 30 patients with ICDs, will be treated with 18 mg per day of nalmefene during 3 months.

Patients will be evaluated 2 times: at inclusion visit (J0) and 3 months after (at the end of the study, +3months).

At each time, patients will have :

• a clinical and neurological evaluation
• neuropsychological tests for cognitive, depression and TCI evaluations.
• blood sample to test hepatic and renal functions
• tolerance evaluation with a list of adverse events/effects

Patients will be contacted 3 times by phone: 2 weeks after inclusion, 1 month after inclusion and 2 months after inclusion, to note the presence of adverse events.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Clermont-ferrand, France, 63003
    • CHU Clermont-Ferrand

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient suffering of Parkinson's disease
• Male or Female aged from 18 to 80 years old
• Diagnosis of ICDs with the Ardouin Scale of Behavior in Parkinson's Disease (ASBPD) with a score of at least 2 on one of the Item of hyperdopaminergic symptoms
• No modification of the treatments for PD since 3 months
• No modification of parameters of deep brain stimulation since 6 months
• Patients who understood and signed the consent form
• Patients having a social security

Exclusion Criteria:

• Contraindication to nalmefene (Patients receiving opioid antalgics, antecedent of opioid dependence, dopamine agonist withdrawal syndrome, opioid consumption, patient receiving methadone or buprenorphine, severe hepatic failure, severe renal failure, antecedent of alcohol withdrawal, galactose intolerance, lactose deficit or glucose malabsorption, pregnant women)
• Cognitive impairment with Mini Mental Score < 26
• Psychiatric comorbidities (bipolar disease, schizophrenia)
• Patient participating in another therapeutic study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: nalmefene	Drug: Nalmefene; 30 patients with ICDs, will be treated with 18 mg per day of nalmefene during 3 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Tolerance of Nalmefene measured by the dropout rate secondary to adverse effects	at + 3months
Efficacy of Nalmefene measured by the change from baseline of the QUIP-RS	at + 3months

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline of the cognitive state assessed by the Montreal Cognitive Assessment scale	at +3 months
Change from baseline of the depression assessed by the Hamilton scale	at +3 months
Change from baseline of the motor severity assessed by the Unified Parkinson Disease Rating Scale at +3 months	at +3 months
Change from baseline of hepatic and renal function evaluated with blood samples at +3 months	at +3 months

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand

Study record dates

Study Major Dates

• Study Start: December 1, 2016
• Primary Completion (ANTICIPATED): March 1, 2018
• Study Completion (ANTICIPATED): May 1, 2018

Study Registration Dates

• First Submitted: October 14, 2016
• First Submitted That Met QC Criteria: October 14, 2016
• First Posted (ESTIMATE): October 17, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): October 17, 2016
• Last Update Submitted That Met QC Criteria: October 14, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Efficacy; Tolerance; Parkinson's disease; Impulse control disorders; Nalmefene
• 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; Nalmefene
• Other Study ID Numbers: CHU-0286; 2016-002805-21 (OTHER: 2016-002805-21)