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

• motor scale [ Time Frame: at 3, 6, 9 and 12 month ] [ Designated as safety issue: Yes ]
• Psychiatric scale [ Time Frame: at 3, 6, 9 and 12 month ] [ Designated as safety issue: Yes ]
• cognitive function scale [ Time Frame: at 3, 6, 9 and 12 month ] [ Designated as safety issue: Yes ]
• metabolic parameters [ Time Frame: at 3, 6, 9 and 12 month ] [ Designated as safety issue: Yes ]
• tolerance [ Time Frame: at 3, 6, 9 and 12 month ] [ Designated as safety issue: Yes ]
• cost [ Time Frame: at 3, 6, 9 and 12 month ] [ Designated as safety issue: Yes ]

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.

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, psychiatric and cognitive functions, metabolic parameters, tolerance and cost.

• Drug: Zyprexa
  Zyprexa VELOTABS (Olanzapine) oral dispersible form 5 to 10 mg / 5 à 20 mg per day
  Other Name: olanzapine
• Drug: Xenazine
  Xenazine (tetrabenazine) tabs of 25mg , from 25 mg to 200 mg
  Other Name: tetrabenazine
• Drug: Tiapride
  Tiapride (Tiapridal), tabs 100 mg / from 300 to 800 mg per day
  Other Name: tiapridal

• Experimental: 1
  zyprexa
  Intervention: Drug: Zyprexa
• Active Comparator: 2
  Xenazine
  Intervention: Drug: Xenazine
• Active Comparator: 3
  Tiapride
  Intervention: Drug: Tiapride

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 ≤ CAG (amendment n°5 suppressed the limit ≤ 48)
3. Neuroleptic Prescription required.
4. Age between ≥ 18 (amendment n°5 suppressed the limit ≤ 65 ans)
5. Patient gave its written consent

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 RCT.
5. No drug compliance to previous treatment.
6. No national health insurance affiliation