ID-CLO: Study of Clonidine Efficacy for the Treatment of Impulse Control Disorders in Parkinson's Disease:

Sponsor

Hospices Civils de Lyon (Other)

Overall Status

Completed

CT.gov ID

NCT03552068

Collaborator

(none)

Enrollment

Location

Arms

30.7

Actual Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Noradrenergic system is involved in impulsivity in the general population and is altered in Parkinson's disease (PD) in the early stages of the disease. Thus, targeting this system could be of interest in impulse control disorder (ICD). Acting on the noradrenergic system is possible using clonidine, an α2 adrenergic agonist largely used in hypertension treatment and that induces a decrease of NADR release. Thus, our aim is to conduct a proof of concept study evaluating the efficacy and safety of clonidine on ICD in PD. This study is a multicenter, randomized, double-blind, placebo-controlled in parallel group clinical trial.

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease Mpulse Control Disorders	Drug: placebo Drug: Clonidine	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

38 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Study of Clonidine Efficacy for the Treatment of Impulse Control Disorders in Parkinson's Disease: A Pilot Double Blind Randomized Trial

Actual Study Start Date :

May 15, 2019

Actual Primary Completion Date :

Jul 15, 2021

Actual Study Completion Date :

Dec 3, 2021

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Patients under placebo Treatment will be taken during 8 weeks with one visit at 2, 4 and 8 weeks. The usual antiparkinsonian treatment of the patient should remain stable throughout the 8 weeks.	Drug: placebo Treatment (placebo) will be taken during 8 weeks with one visit at 2, 4 and 8 weeks. Medication: placebo twice a day (in the morning and evening).
Active Comparator: Patient under clonidine Treatment will be taken during 8 weeks with one visit at 2, 4 and 8 weeks. The usual antiparkinsonian treatment of the patient should remain stable throughout the 8 weeks.	Drug: Clonidine Treatment will be taken during 8 weeks with one visit at 2, 4 and 8 weeks. Medication: 75 μg of clonidine twice a day (in the morning and evening).

Arm

Intervention/Treatment

Placebo Comparator: Patients under placebo

Treatment will be taken during 8 weeks with one visit at 2, 4 and 8 weeks. The usual antiparkinsonian treatment of the patient should remain stable throughout the 8 weeks.

Drug: placebo

Treatment (placebo) will be taken during 8 weeks with one visit at 2, 4 and 8 weeks. Medication: placebo twice a day (in the morning and evening).

Active Comparator: Patient under clonidine

Treatment will be taken during 8 weeks with one visit at 2, 4 and 8 weeks. The usual antiparkinsonian treatment of the patient should remain stable throughout the 8 weeks.

Drug: Clonidine

Treatment will be taken during 8 weeks with one visit at 2, 4 and 8 weeks. Medication: 75 μg of clonidine twice a day (in the morning and evening).

Outcome Measures

Primary Outcome Measures

QUIP-RS (Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease - Rating Scale) [at 8 weeks]
Diminution of impulse control disorder severity on the initial more elevated sub-score of the QUIP-RS between the first visit and the eighth week under clonidine. Diminution of impulse control disorder severity on the initial more elevated sub-score of the QUIP-RS between the first visit and the eighth week under clonidine. Diminution of impulse control disorder severity on the initial more elevated sub-score of the QUIP-RS between the first visit and the eighth week under clonidine.

Secondary Outcome Measures

MDS-UPDRS [at 4 and 8 weeks]
The Movement Disorder Society Unified Parkinson Disease Rating
STAI [at 4 and 8 weeks]
State-Trait Anxiety Index
BDI II [at 4 and 8 weeks]
Beck Depression Inventory II It is a self-administered questionnaire each of them using a four-point ordinal scoring system. For the summary index the scores were standardized from 1 to 40, so that higher scores indicate higher depression.
ECMP scores [at 4 and 8 weeks]
Behavior evaluation of Parkinson's patients It is a self-administered questionnaire each of them using a four-point ordinal scoring system. For the summary index the scores were standardized from 1 to 40, so that higher scores indicate higher depression.
QUIP-RS sub-scores [at 4 weeks]
Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease - Rating Scale Diminution of impulse control disorder severity on the initial more elevated sub-score of the QUIP-RS between the first visit and the fourth weeks under clonidine. It is a self-administered questionnaire. For the summary index the scores were standardized from 1 to 112, so that higher scores indicate higher Impulse control disorder. The sub score are standardized between 0 and 16.
QUIP-RS total score [at 4 and 8 weeks]
Evolution of QUIP-RS total score and sub-scores Diminution of impulse control disorder severity on total score of the QUIP-RS between the first visit, the fourth and the eighth weeks under clonidine. It is a self-administered questionnaire. For the summary index the scores were standardized from 1 to 112, so that higher scores indicate higher Impulse control disorder.
PDQ 39 scale (Parkinson Disease Quotation) [at 4 and 8 weeks]
It is a self-administered questionnaire comprised of 39 questions, each of them using a five-point ordinal scoring system, from which a single summary index can be calculated. For the summary index the scores were standardized from 0 to 100, so that higher scores indicate poorer quality of life.

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with PD according to MDS (movement disorders society) criteria for at least one year
Patients with ICD with a QUIP-RS score ≥10 and/or at least one of the sub-scores in the following range: Pathological gambling between >6 and 12; Pathological gambling between >8 and 12; Hypersexuality between > 8 and 12; Eating between > 7 and 12. The use of "lower" margins will guarantee that patients will present behavioral disturbances severe enough to justify clonidine treatment. On the other hand, the use of "upper" margins will guarantee that the patients included in the trial will not suffer from ICD too severe to ethically participate to a placebo controlled study.
Weight between 40 and 95kg
Stable antiparkinsonian medication since at least 2 months before randomization and medication supposed to remain stable during the study
ICD onset after Parkinson's disease onset and after initiation of dopaminergic drugs
No signs of dementia (Montreal Cognitive Assessment, MOCA >20);
No lactose intolerance which may compromise the tolerance of the placebo;
Patients with health insurance
Patients without judicial protection measure except directly linked to ICD
For women of childbearing potential, an effective contraception method for at least 2 months before randomization (as implants or oral oestro-progestative contraceptives), condom use for men during the study. βHCG dosage in urine should be negative at randomization for women.

Exclusion Criteria:

Patients with major depression (BDI >19);

Patients with another parkinsonian syndrome (Parkinson "plus" or vascular Parkinsonism)
Orthostatic hypotension
Patients with swallowing disorders that may prevent oral medication,
Contraindication to clonidine: Hypersensibility; Severe bradyarythmia due to a cardiac disease
Patients receiving a treatment potentially interacting with clonidine
Patients with Raynaud's disease or obliterating thromboangiitis
Patients With Heart failure or severe coronary artery disease
Patients with a drug treatment having a potential interaction with clonidine (see list, appendix 2);
Presence of renal failure (Cockcroft-Gault at inclusion visit<30 ml/min/1,73m2);
Patients with a present or past history of addiction (apart ICD) or with a substance abuse (except Tabaco)
Pregnant or lactating women
Already participating in another biomedical research project