Topiramate and Schizophrenia: Effects on Weight and Psychopathology

Schizophrenia, Schizoaffective Disorder Clinical Trial

Official title:

Topiramate in Treatment Refractory Psychotic Illness: Effects on Weight Gain and Psychopathology

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02808533
• Other study ID #: 097/2015
• Status: Recruiting
• Phase: N/A
• Start date: May 2016
• Est. completion date: July 2024

Study information

• Verified date: July 2023
• Source: Centre for Addiction and Mental Health
• Contact: Margaret Hahn, PhD, MD
• Phone: 416-535-8501
• Email: margaret.hahn[@]camh.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: July 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 17 Years to 59 Years

Eligibility

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

Related Conditions & MeSH terms

• Psychotic Disorders
• Schizophrenia
• Schizophrenia, Schizoaffective Disorder

Intervention

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:
• Placebo
Placebo capsules visually identical to those containing topiramate will be administered.

Locations

Country	Name	City	State
Canada	Center for Addiction and Mental Health	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Centre for Addiction and Mental Health	Ontario Ministry of Health and Long Term Care

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Visceral adiposity changes	Measured through MRI	Baseline and 16 weeks
Other	Cognition - Brief Assessment of Cognition in Schizophrenia (BACS)	A standardized assessment of cognitive in patients with schizophrenia	16 weeks
Other	Volumetric Brain changes	Measured through MRI	Baseline and 16 weeks
Other	Hepatic adiposity changes	Measured through MRI	Baseline and 16 weeks
Primary	Weight loss	Measured in pounds	16 weeks
Secondary	Insulin sensitivity	Measured through Oral Glucose Tolerance Test (pmol/L)	16 weeks
Secondary	Psychopathology - Positive and Negative Syndrome Scale (PANSS)	Anchored scale to rate positive and negative psychiatric symptoms	16 weeks
Secondary	Glucose Tolerance	Measured through Oral Glucose Tolerance Test (mmol/L)	16 weeks
Secondary	Psychopathology - Brief Psychiatric Rating Scale (BPRS)	Anchored rating scale for psychiatric symptoms	16 weeks
Secondary	Psychopathology - Clinical Global Impression (CGI)	Anchored scale to rate global impression of patient	16 weeks
Secondary	Psychopathology - Global Assessment of Functioning (GAF)	Anchored scale to rate global functioning of patient	16 weeks

External Links

•   The Centre for Addiction and Mental Health (CAMH) is the leading mental health and addictions research facility in Canada, and one of the largest in the world.