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

• Status: Terminated
• Trial end date: 2016-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Treatments: Topiramate

Criteria

Inclusion Criteria:

1. Patient with Prader Willi syndrome confirmed by genetic diagnosis.

2. Patient has at least one of the following symptoms:

• Presence of self-harm

• Impulsive and / or aggressive

• Trouble eating and / or obesity

3. Age between 12 and 45 years inclusive

4. Weight higher than 50 kg

5. Signature of consent by the patient or the holders of parental authority (or legal guardian)

Non inclusion criteria:

1. Meeting the criteria according to DSM IV Schizophrenia

2. Presence of hallucination (SAPS scales and scale of hallucination)

3. Already has an effective dose of topiramate for a sufficient time and without efficiency

4. Psychotropic introduced for less than three months or dose change for less than three months.

5. Psychotropic stopped for less than a month, or three months in the case of fluoxetine.

6. Inability to find an informative adult in the subject's behavior.

7. Known hypersensitivity to one of topiramate constituents or its placebo

8. Known hypersensitivity to sulfonamides

9. Epilepsy associated or taking other anticonvulsant or mood stabilizer.

10. Medication with St. John's wort

11. No affiliation to a social security

12. Patient known to be non-compliant

13. Subject to suicide risk

14. Severe depression

15. Previous history of nephrolithiasis or glaucoma

16. Poorly controlled diabetes (A1C greater than 10%) treated with metformin or Gibenclamide.

17. Patients with rare hereditary problems of fructose intolerance, glucose malabsorption or galactose or sucrose-isomaltase insufficiency (because of the presence of sucrose)

18. Pregnant or breastfeeding

19. Lack of effective contraception among patients of childbearing potential

Exclusion criteria before randomization:

• 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)