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Topiramate and Schizophrenia: Effects on Weight and Psychopathology

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ClinicalTrials.gov Identifier: NCT02808533
Recruitment Status : Recruiting
First Posted : June 21, 2016
Last Update Posted : January 9, 2020
Sponsor:
Collaborator:
Ontario Ministry of Health and Long Term Care
Information provided by (Responsible Party):
Margaret Hahn, Centre for Addiction and Mental Health

Brief Summary:
Clozapine is the sole AP agent with superiority in treatment refractory schizophrenia, but it also is associated with the greatest risk of weight gain and other metabolic abnormalities. Topiramate, an anticonvulsant agent, possesses a weight-reducing effect. Furthermore, some studies have suggested that Topiramate may be associated with improvements in psychopathology in treatment refractory schizophrenia. Here the investigators propose to determine the role of topiramate for augmentation purposes (psychopathology) and as an adjunctive pharmacological intervention for weight loss in overweight/obese individuals with Ultra-Treatment Resistant Schizophrenia or Schizoaffective disorder taking clozapine.

Condition or disease Intervention/treatment Phase
Schizophrenia, Schizoaffective Disorder Drug: Topiramate Other: Placebo Not Applicable

Detailed Description:

Schizophrenia is a chronic illness characterized by social and vocational disruptive functioning. While >70% of individuals with first episode illness respond to antipsychotics (APs), there remains a subgroup left with persisting psychotic symptoms. For these individuals, clozapine (CLZ) is also the sole drug with treatment superiority, but also carries the greatest metabolic liability. Another complicating factor in those treated with CLZ is the observation that while effective in some, 40-70% of individuals fail to show significant improvement with CLZ, often leading to augmentation strategies. While controlled trials are, in general lacking, a number of agents have been suggested as useful. One such group of medications includes the anticonvulsants.

Topiramate represents one of the newer anticonvulsant agents approved for the treatment of epilepsy and prophylaxis of migraines. Importantly, topiramate possesses a weight-reducing effect that has been substantiated by a meta-analysis in non-psychiatric patients. Interestingly, topiramate has been studied as an adjunctive therapy in treatment-resistant schizophrenia with some evidence demonstrating small to moderate benefits with topiramate augmentation on psychopathology. However, these benefits must also be weighed against reports (primarily from epilepsy populations), that topiramate may cause cognitive dysfunction.

This study will examine:

  1. Topiramate-related effects on weight
  2. Topiramate-related effects on glucose tolerance and insulin sensitivity
  3. Topiramate-related effects on psychopathology and cognition
  4. Topiramate-related effects on adiposity

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Topiramate in Treatment Refractory Psychotic Illness: Effects on Weight Gain and Psychopathology
Actual Study Start Date : May 2016
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : March 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Topiramate

Arm Intervention/treatment
Experimental: Topiramate
Topiramate will be dispensed on a biweekly basis, and pill counts conducted at each visit.
Drug: Topiramate
Topiramate capsules starting with 25 mg b.i.d with an incremental increase of 25 mg b.i.d weekly upto a maximum of 100 mg b.i.d.
Other Name: Topamax

Placebo Comparator: Placebo
Placebo will be dispensed on a biweekly basis, and pill counts conducted at each visit.
Other: Placebo
Placebo capsules visually identical to those containing topiramate will be administered.




Primary Outcome Measures :
  1. Weight loss [ Time Frame: 16 weeks ]
    Measured in pounds


Secondary Outcome Measures :
  1. Insulin sensitivity [ Time Frame: 16 weeks ]
    Measured through Oral Glucose Tolerance Test (pmol/L)

  2. Psychopathology - Positive and Negative Syndrome Scale (PANSS) [ Time Frame: 16 weeks ]
    Anchored scale to rate positive and negative psychiatric symptoms

  3. Glucose Tolerance [ Time Frame: 16 weeks ]
    Measured through Oral Glucose Tolerance Test (mmol/L)

  4. Psychopathology - Brief Psychiatric Rating Scale (BPRS) [ Time Frame: 16 weeks ]
    Anchored rating scale for psychiatric symptoms

  5. Psychopathology - Clinical Global Impression (CGI) [ Time Frame: 16 weeks ]
    Anchored scale to rate global impression of patient

  6. Psychopathology - Global Assessment of Functioning (GAF) [ Time Frame: 16 weeks ]
    Anchored scale to rate global functioning of patient


Other Outcome Measures:
  1. Visceral adiposity changes [ Time Frame: Baseline and 16 weeks ]
    Measured through MRI

  2. Cognition - Brief Assessment of Cognition in Schizophrenia (BACS) [ Time Frame: 16 weeks ]
    A standardized assessment of cognitive in patients with schizophrenia

  3. Volumetric Brain changes [ Time Frame: Baseline and 16 weeks ]
    Measured through MRI

  4. Hepatic adiposity changes [ Time Frame: Baseline and 16 weeks ]
    Measured through MRI



Information from the National Library of Medicine

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Ages Eligible for Study:   17 Years to 59 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Schizophrenia or Schizoaffective disorder
  • 17-59 years of age
  • Clozapine treatment for at least 12 weeks at a dose 350 mg/d or greater and/or plasma clozapine levels of 300 ng/mL or greater
  • CGI must be 4 or higher and/or GAF < 50
  • BMI greater than or equal to 25

Exclusion Criteria:

  • Alcohol use disorder
  • Patients with liver, or renal dysfunction
  • Females of child bearing age not on a regular contraceptive, females who are nursing
  • Clinical or laboratory evidence of uncompensated cardiovascular, endocrine, hematological, or pulmonary disease.
  • HbA1c > 9%, or symptomatic hyperglycemia with metabolic decompensation
  • Prior lack of efficacy or tolerability of Topiramate
  • Addition of new hypoglycemic or lipid lowering medication within 2 months of starting study
  • Patients treated with Valproic Acid
  • Patients treated with hydrochlorothiazide
  • Switch in antipsychotic medications within 3 months of study entry
  • Major medical or surgical event within the preceding 3 months
  • History of renal stones
  • Use of Carbonic Anhydrase Inhibitor
  • History of glaucoma
  • Acute Suicidal risk

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): NCT02808533


Contacts
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Contact: Margaret Hahn, PhD, MD 416-535-8501 ext 34368 margaret.hahn@camh.ca
Contact: Quinn A Casuccio-Treen, BSc 416-535-8501 ext 34719 quinn.treen@camh.ca

Locations
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Canada, Ontario
Center for Addiction and Mental Health Recruiting
Toronto, Ontario, Canada, M5T 1R8
Contact: Margaret K Hahn, MD    4165358501 ext 34368    margaret.hahn@camh.ca   
Contact: Quinn A Casuccio-Treen, HBSc    4165358501 ext 34719    quinn.treen@camh.ca   
Principal Investigator: Margaret K Hahn, MD, PhD         
Sponsors and Collaborators
Centre for Addiction and Mental Health
Ontario Ministry of Health and Long Term Care
Investigators
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Principal Investigator: Margaret Hahn, PhD, MD Centre for Addiction and Mental Health
Additional Information:
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Responsible Party: Margaret Hahn, Clinician-Scientist, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier: NCT02808533    
Other Study ID Numbers: 097/2015
First Posted: June 21, 2016    Key Record Dates
Last Update Posted: January 9, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Schizophrenia
Psychotic Disorders
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Topiramate
Anticonvulsants
Hypoglycemic Agents
Physiological Effects of Drugs