Neuroleptic and Huntington Disease Comparison of : Olanzapine, la Tetrabenazine and Tiapride (NEUROHD)

Neuroleptic and Huntington Disease. Comparison of : Olanzapine, la Tetrabenazine and Tiapride. A Multicentric, Randomised, Controlled Study.

Huntington's disease (HD) is autosomal dominant neurodegenerative disease, starting in average (with high variability) in the fourth decade. The disease progression is classically characterized by a cognitive deterioration (cortical-frontal dementia), motor disorders (associating chorea, dystonia and bradykinesia), psychiatric disturbances (combining depression and irritability) and metabolic disorder (cachexia). The disease is fatal within 15 to 20 years in most patients. HD has no cure. Neuroleptics are the main drug used and the only to demonstrate its efficacy on chorea in clinical trials. But neuroleptics have also beneficial and adverse effects on other disease characteristics (motor, psychiatric, cognitive or metabolic). Their profile between beneficial and adverse effects could be different according the neuroleptics and their classification. The aim of this study is to compare beneficial and adverse effects of 3 different neuroleptics in HD.

Study Overview

• Status: Completed
• Conditions: Huntington Disease
• Intervention / Treatment: Drug: Olanzapine; Drug: Xenazine; Drug: Tiapridal

Detailed Description

We proposed a randomized controlled trial, including 180 patients, in 3 groups: Olanzapine, Tetrabenazine and Tiapride, followed during 12 months. These treatments have been selected according their profile and their frequency of use.

The principal criteria is the Independence scale, one of the functional scales of the Unified Huntington's Disease Rating Scale, the only validated scale in HD.

Secondary criteria will assess motor,functional, psychiatric and cognitive functions, metabolic parameters, tolerance and cost.

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Creteil, France, 94
    • CHU Henri Mondor

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Symptomatic disease with motor, behavioural and/or psychiatric disorder required medical treatment.
2. HD diagnosed with abnormal number of CAG repeats: 38 ≤ nucleotide expansion (CAG) (amendment n°5 suppressed the limit ≤ 48)
3. Neuroleptic Prescription required.
4. Age ≥ 18 (amendment n°5 suppressed the limit ≤ 65 years old)
5. Patient gave its written consent
6. Realization of medical examination and a Electroencephalogram

Exclusion Criteria:

1. Severe cognitive impairment or neuropsychiatric troubles.
2. Existing diabetes.
3. Neuroleptic prescription forbidden according to the neurologist decision.
4. Current participation to another clinical trial.
5. No drug compliance to previous treatment.
6. No national health insurance affiliation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Olanzapine Mylan	Drug: Olanzapine; Olanzapine Mylan oral dispersible form 5 to 10 mg / 2,5 à 20 mg per day; Other Names: Olanzapine Mylan
Active Comparator: 2; Xenazine	Drug: Xenazine; Xenazine (tetrabenazine) tabs of 25mg , from 25 mg to 200 mg; Other Names: tetrabenazine
Active Comparator: 3; Tiapridal	Drug: Tiapridal; Tiapridal (Tiapride), tabs 100 mg / from 300 to 800 mg per day; Other Names: tiapride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
the Independence scale	at 12 month

Secondary Outcome Measures

Outcome Measure	Time Frame
motor scale	at 3, 6, 9 and 12 month
Psychiatric scale	at 3, 6, 9 and 12 month
cognitive function scale	at 3, 6, 9 and 12 month
metabolic parameters	at 3, 6, 9 and 12 month
tolerance	at 3, 6, 9 and 12 month
cost	at 3, 6, 9 and 12 month
Function scale (TFC and Functionnal Appreciation Scale)	at 3, 6, 9 and 12 month

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Anne-Catherine BACHOUD LEVI, PH, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2009
• Primary Completion (Actual): April 28, 2017
• Study Completion (Actual): April 28, 2017

Study Registration Dates

• First Submitted: February 29, 2008
• First Submitted That Met QC Criteria: March 10, 2008
• First Posted (Estimate): March 11, 2008

Study Record Updates

• Last Update Posted (Actual): January 19, 2018
• Last Update Submitted That Met QC Criteria: January 18, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Neuroleptic; Huntington; Unified Huntington Disease Rating Scale (UHDRS); Independence Scale; Neuroleptic Prescription required
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Dementia; Cognition Disorders; Chorea; Huntington Disease; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Dopamine Agents; Dopamine Antagonists; Adrenergic Uptake Inhibitors; Olanzapine; Tetrabenazine; Tiapride Hydrochloride
• Other Study ID Numbers: P060211