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

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ClinicalTrials.gov Identifier: NCT02810483
Recruitment Status : Terminated
First Posted : June 23, 2016
Last Update Posted : April 11, 2018
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

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.

Condition or disease Intervention/treatment Phase
Prader-Willi Syndrome Drug: Topiramate Drug: Placebo Comparator Phase 3

Show Show detailed description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 69 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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 Prader Willi Syndrome Over 8 Weeks
Study Start Date : December 2012
Actual Primary Completion Date : November 2015
Actual Study Completion Date : June 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Topiramate

Arm Intervention/treatment
Experimental: Arm 1: Topiramate
Topiramate Arrow 50 mg hard capsules
Drug: Topiramate

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.

Other Name: Topiramate Arrow generic

Placebo Comparator: Arm 2: Placebo Comparator
50 mg hard capsules with the same shape, color and taste than the active product
Drug: Placebo Comparator

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.





Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Weight and size [ Time Frame: at 8 weeks (endpoint) ]
    Weight and size (BMI in kg/m2)

  2. Self-Injury Behavior Scale ECAHA, [ Time Frame: at 8 weeks (endpoint) ]
    Comparison between baseline score and endpoint score

  3. Self-Injury Behavior, CONNERS Impulsivity [ Time Frame: at 8 weeks (endpoint) ]
    CONNERS Impulsivity comparison between baseline score and endpoint score

  4. Self-Injury Behavior,Dickens [ Time Frame: at 8 weeks (endpoint) ]
    Dickens comparison between baseline score and endpoint score

  5. C-SHARP (Chid and Adolescent), appearance of positive suicide item response [ Time Frame: at 8 weeks (endpoint) ]
  6. A-SHARP (Adult), appearance of positive suicide item response [ Time Frame: at 8 weeks (endpoint) ]
    A-SHARP (Adult), appearance of positive suicide item response

  7. 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.

  8. 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



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Ages Eligible for Study:   12 Years to 45 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02810483


Locations
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France
Hôpital La Pitié Salpêtrière
Paris, France, 75013
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
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Principal Investigator: Olivier BONNOT, PhD, MD Assistance Publique - Hôpitaux de Paris
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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT02810483    
Other Study ID Numbers: AOM10088
First Posted: June 23, 2016    Key Record Dates
Last Update Posted: April 11, 2018
Last Verified: April 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Prader-Willi
SPW
impulsivity
eating disorders
topiramate
Additional relevant MeSH terms:
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Prader-Willi Syndrome
Syndrome
Disease
Pathologic Processes
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn
Obesity
Overnutrition
Nutrition Disorders
Topiramate
Anticonvulsants
Hypoglycemic Agents
Physiological Effects of Drugs