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

Study Overview
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Brief Summary
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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.

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

Conditions
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Parkinson's Disease, Mpulse Control Disorders

Intervention / Treatment
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* Drug: placebo
* Drug: Clonidine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Patients under placebo<br>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<br>* 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).<br>|
| Active Comparator: Patient under clonidine<br>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<br>* 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).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| QUIP-RS (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 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. | at 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MDS-UPDRS | The Movement Disorder Society Unified Parkinson Disease Rating | at 4 and 8 weeks | 
| STAI | State-Trait Anxiety Index | at 4 and 8 weeks | 
| BDI II | 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. | at 4 and 8 weeks | 
| ECMP scores | 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. | at 4 and 8 weeks | 
| QUIP-RS sub-scores | 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. | at 4 weeks | 
| QUIP-RS total score | 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. | at 4 and 8 weeks | 
| PDQ 39 scale (Parkinson Disease Quotation) | 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. | at 4 and 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's disease, Impulse control disorder, Clonidine, Noradrenergic system