Clinical Trial: Study of the Efficacy of Topiramate in Patients With Prader Willi Syndrome Over 8 Weeks

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Randomized, Placebo Controlled Double-blind Study of the Efficacy of Topiramate on the Symptoms of Irritability - Impulsivity, Overeating and Self-harm in a Population of Patients Suffering From

Brief Summary:

There is no specific treatment for core symptoms of PWS. Regarding behavioral and psychiatric symptoms (hyperphagia, imulsivity and self-mutilations), one of the only drug options consists in antipsychotics, that are not efficient and might be responsible for a worsening of the weight gain (major issue in PWS). An alternative therapeutic approach for behavioral disturbances has been suggested by some authors with topiramate (Epitomax®), an antiepileptic drug that can be used as a mood stabilizer and anti-impulsive. In addition, topiramate is used as a treatment for eating disorders because it induces loss of weight and appetite. This last effect might be useful in the case of SPW.

Except for some clinical case reports, the investigators only found one open study for topiramate in SPW 8 patientssuggesting promising effects. There si however no placebo controlled study..

Objective:

To evaluate the efficacy of topiramate (200 mg / d) on Eating disorders (E), self Mutilations (M), irritability and Impulsivity (I), metabolic status, and tolerance among of PWS patients.

Methodology:

This is a multicenter (out-patients in Toulouse, Reims, Nantes and Paris and in-patients in Hendaye) 8 weeks double-blind placebo controlled study .

Subjects (n = 125 for 112 analyzable) all having PWS, aged 12 years-old and more should have any of the following symptoms: E, M and U (see above). All subjects will be randomly allocated into two groups one taking a placebo, the other taking topiramate (50mg / day initially, increasing up to 50mg per week 200mg / day).

The population of analyzable patie

Detailed Summary:

Scientific background and justification of the study :

Patients with a rare disease are often challenging to treat when considering psychotropic treatment for behavioral or psychiatric manifestations. There is an important lack of clear data or treatment guidelines for treating behavioral disturbance in patients with intellectual disabilities. Prader Willi syndrome (PWS) is a paradigmatic example of such a disease. It is a rare disease with an estimated prevalence of 1:25,000 at birth. PWS is a genetic disease located on chromosome 15 (15 q11-q13). Imprinting silence the normal genes on 15 q11-Q13, rendering them non-functional, with the paternal non-imprinted genes being deleted. The imprinting effect in this region explains why approximately 60 to 70% of patients with PWS have a paternal deletion of 15q11-q13 (2). An additional 25 to 35 % of patients have two copies of maternal chromosome 15 (uniparental disomy). Rarely, PWS may be associated with translocation, mutation, or other anomalies. Angelman Syndrome, which has primarily been associated with autism spectrum disorders, involves the same genetic region and is commonly associated to mutations of the maternal allele of the UB3a gene or rare deletions. .

PWS patients present in a neonatal hypotonic state with deficit of sucking and eating refusal which progresses to with hyperphagia and obsession with food in infancy or adolescence. In addition, patients have distinct facial features, such as a narrow forehead, almond-shaped eyes, and a triangular mouth, as well as a short stature, related to growth hormone deficiency and small hands and feet. Puberty is often delayed or incomplete, and most affected individuals are unable to have children. This eating disorder is more similar to an addictive disorder to food than a traditional eating disorder. PWS leads to severe ob
Sponsor: Assistance Publique - Hôpitaux de Paris

Current Primary Outcome: Clinical Global Impression Improvement [ Time Frame: at 8 weeks (endpoint) ]

Endpoint CGI score at 1 or 2 will make consider the patient as a responder. A 7 items scale will be used


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Weight and size [ Time Frame: at 8 weeks (endpoint) ]
    Weight and size (BMI in kg/m2)
  • Self-Injury Behavior Scale ECAHA, [ Time Frame: at 8 weeks (endpoint) ]
    Comparison between baseline score and endpoint score
  • Self-Injury Behavior, CONNERS Impulsivity [ Time Frame: at 8 weeks (endpoint) ]
    CONNERS Impulsivity comparison between baseline score and endpoint score
  • Self-Injury Behavior,Dickens [ Time Frame: at 8 weeks (endpoint) ]
    Dickens comparison between baseline score and endpoint score
  • C-SHARP (Chid and Adolescent), appearance of positive suicide item response [ Time Frame: at 8 weeks (endpoint) ]
  • A-SHARP (Adult), appearance of positive suicide item response [ Time Frame: at 8 weeks (endpoint) ]
    A-SHARP (Adult), appearance of positive suicide item response
  • Safety Assessment [ Time Frame: at 8 weeks (endpoint) ]
    The proportion of patients stopped the treatment, of patients with adverse events and prematurely discontinued treatment due to an adverse event will be estimated.
  • Biological assessment [ Time Frame: at 8 weeks (endpoint) ]
    The number of patients with abnormal values and / or modified from the baseline values will be evaluated


Original Secondary Outcome: Same as current

Information By: Assistance Publique - Hôpitaux de Paris

Dates:
Date Received: May 17, 2016
Date Started: December 2012
Date Completion:
Last Updated: June 22, 2016
Last Verified: April 2016