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

NCT02810483 | Terminated Phase 3

• 1 other identifier: AOM10088
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

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 patients in and out patient will be of equal size (n = 56). The inclusion period is two years.. Are excluded subjects with antipsychotic or mood stabilizer medication or topiramate. The primary endpoint will be the rate of responders, with response defined by obtaining a score of 1 or 2 on the CGI improvement after 8 weeks of treatment Other assessments, secondary endpoints :

• Clinic: Weight / Size / Self-injury behavior (french Echelle des Conduites Auto et Hétéro Aggressives, ECAHA))
• Psychometric: C-SHARP and A-SHARP / Conners (Impulsivity) / Dickens (Eating behavior for PWS)
• Organic: NFS, serum electrolytes, creatinine, ammonia plasma, serum bicarbonate, AST / ALT / GGT, ghrelin, fasting glucose, lipid profile and insulin, leptin, TG and HbA1c.
• Side effects of topiramate: SAPS / SANS and BPRS (hallucinations), anxiety scales and laboratory tests.

Conditions

Prader-Willi Syndrome

Keywords

Prader-Willi; SPW; impulsivity; eating disorders; topiramate

Outcome Measures

Primary Outcomes (1)

• Clinical Global Impression Improvement

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

  at 8 weeks (endpoint)

Secondary Outcomes (8)

• Weight and size

  at 8 weeks (endpoint)

• Self-Injury Behavior Scale ECAHA,

  at 8 weeks (endpoint)

• Self-Injury Behavior, CONNERS Impulsivity

  at 8 weeks (endpoint)

• Self-Injury Behavior,Dickens

  at 8 weeks (endpoint)

• C-SHARP (Chid and Adolescent), appearance of positive suicide item response

  at 8 weeks (endpoint)

Study Arms (2)

Arm 1: Topiramate

EXPERIMENTAL

Topiramate Arrow 50 mg hard capsules

Drug: Topiramate

Arm 2: Placebo Comparator

PLACEBO COMPARATOR

50 mg hard capsules with the same shape, color and taste than the active product

Drug: Placebo Comparator

Interventions

Topiramate DRUG

Increase phase. The starting dose is 50 mg / day with gradual increase in dose to 50 mg / week until the end of the 3rd week. Dose of study: 200mg for 5 weeks. Decrease phase: The 9th week, 100mg for 4 days then 50mg for 3 days.

Also known as: Topiramate Arrow generic

Arm 1: Topiramate

Placebo Comparator DRUG

ncrease phase. The starting dose is 50 mg / day with gradual increase in dose to 50 mg / week until the end of the 3rd week. Dose of study: 200mg for 5 weeks. Decrease phase: The 9th week, 100mg for 4 days then 50mg for 3 days.

Arm 2: Placebo Comparator

Eligibility Criteria

• Age: 12 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patient with Prader Willi syndrome confirmed by genetic diagnosis.
• Patient has at least one of the following symptoms:
• Presence of self-harm
• Impulsive and / or aggressive
• Trouble eating and / or obesity
• Age between 12 and 45 years inclusive
• Weight higher than 50 kg
• Signature of consent by the patient or the holders of parental authority (or legal guardian)
• Meeting the criteria according to DSM IV Schizophrenia
• Presence of hallucination (SAPS scales and scale of hallucination)
• Already has an effective dose of topiramate for a sufficient time and without efficiency
• Psychotropic introduced for less than three months or dose change for less than three months.
• Psychotropic stopped for less than a month, or three months in the case of fluoxetine.
• Inability to find an informative adult in the subject's behavior.
• Known hypersensitivity to one of topiramate constituents or its placebo

You may not qualify if:

• Renal failure (serum creatinine greater than 1.5 X normal)
• Hepatic impairment (ALT greater than 2X normal) (
• Anemia (HB \<12 g / dl female \<13g / dl man.)
• Hyper ammonemia (upper normal laboratory)
• Responding to the Schizophrenia criteria according to DSM IV
• Presence of hallucination (SAPS scales and scale of hallucination)
• Decreased serum bicarbonate levels (below the laboratory standards)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hôpital La Pitié Salpêtrière

Paris, 75013, France

Location

MeSH Terms

Conditions

Prader-Willi Syndrome; Impulsive Behavior; Feeding and Eating Disorders

Interventions

Topiramate

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Imprinting Disorders; Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Behavior; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Mental Disorders

Intervention Hierarchy (Ancestors)

Fructose; Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses

Study Officials

• Olivier BONNOT, PhD, MD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2016
• First Posted: June 23, 2016
• Study Start: December 1, 2012
• Primary Completion: November 1, 2015
• Study Completion: June 1, 2016
• Last Updated: April 11, 2018

Record last verified: 2016-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)