Schizophrenia, Schizoaffective DisorderNCT02808533
Topiramate and Schizophrenia: Effects on Weight and Psychopathology
A study testing Topiramate in people with Schizophrenia, Schizoaffective Disorder, run by Centre for Addiction and Mental Health at 1 site in Canada.
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. Read more about this study
- Who is it for?
- Ages 17 to 59 years
- Conditions the study is for
- Schizophrenia, Schizoaffective Disorder
- What is being tested?
- Topiramate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteCanada
- Study dates
- May 2016to Aug 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 17 to 59 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Topiramate in Treatment Refractory Psychotic Illness: Effects on Weight Gain and Psychopathology
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.
Read the 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:
- Topiramate-related effects on weight
- Topiramate-related effects on glucose tolerance and insulin sensitivity
- Topiramate-related effects on psychopathology and cognition
- Topiramate-related effects on adiposity
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Being tested
- Topiramate, Placebo
- Medical subject headings
- Schizophrenia, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TopiramateDrug
Also called Topamax
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.
PlaceboOther
Placebo capsules visually identical to those containing topiramate will be administered.
| Study group | Role | What they receive |
|---|---|---|
| Topiramate | Experimental | Topiramate will be dispensed on a biweekly basis, and pill counts conducted at each visit. Receives: Drug: Topiramate |
| Placebo | Placebo comparator | Placebo will be dispensed on a biweekly basis, and pill counts conducted at each visit. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Weight loss
Measured in pounds
Measured: 16 weeks
Secondary outcomes (6)
Insulin sensitivity
Measured through Oral Glucose Tolerance Test (pmol/L)
Measured: 16 weeks
Psychopathology - Positive and Negative Syndrome Scale (PANSS)
Anchored scale to rate positive and negative psychiatric symptoms
Measured: 16 weeks
Glucose Tolerance
Measured through Oral Glucose Tolerance Test (mmol/L)
Measured: 16 weeks
Psychopathology - Brief Psychiatric Rating Scale (BPRS)
Anchored rating scale for psychiatric symptoms
Measured: 16 weeks
Psychopathology - Clinical Global Impression (CGI)
Anchored scale to rate global impression of patient
Measured: 16 weeks
Psychopathology - Global Assessment of Functioning (GAF)
Anchored scale to rate global functioning of patient
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2016 (estimated)
- Study startMay 2016
- Primary completionAug 2026 (estimated)
- Study completionAug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Schizophrenia, Schizoaffective DisorderStudies of the same condition, open and under way.
- More trials run by Centre for Addiction and Mental HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Collaborators
- Ontario Ministry of Health and Long Term Care
- Responsible party
- Principal investigator, Margaret Hahn, Centre for Addiction and Mental Health
- Investigators
- Margaret Hahn, PhD, MD, Principal investigator, Centre for Addiction and Mental Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02808533
- Sponsor's protocol ID
- 097/2015
- Status last verified
- May 2026
- First submitted
- 15 Jun 2016
- Last updated
- 28 May 2026
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Topiramate in Treatment Refractory Psychotic Illness: Effects on Weight Gain and Psychopathology
- ClinicalTrials.gov ID
- NCT02808533
- Acronym / sponsor ID
- 097/2015
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Collaborators
- Ontario Ministry of Health and Long Term Care
- Study start
- May 2016 (actual)
- Primary completion
- Aug 2026 (estimated)
- Study completion
- Aug 2026 (estimated)
- First posted
- 21 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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:
- Topiramate-related effects on weight
- Topiramate-related effects on glucose tolerance and insulin sensitivity
- Topiramate-related effects on psychopathology and cognition
- Topiramate-related effects on adiposity
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Topiramate | Experimental | Drug: TopiramateTopiramate will be dispensed on a biweekly basis, and pill counts conducted at each visit. |
| Placebo | Placebo comparator | Other: PlaceboPlacebo will be dispensed on a biweekly basis, and pill counts conducted at each visit. |
Who may qualify
- Ages
- 17 to 59 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TopiramateAlso: TopamaxTopiramate 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. | Drug | Topiramate |
| PlaceboPlacebo capsules visually identical to those containing topiramate will be administered. | Other | Placebo |
Primary outcome
Weight loss
Time frame: 16 weeks
Measured in pounds
6 secondary outcomes
Insulin sensitivity
Time frame: 16 weeks
Psychopathology - Positive and Negative Syndrome Scale (PANSS)
Time frame: 16 weeks
Glucose Tolerance
Time frame: 16 weeks
Psychopathology - Brief Psychiatric Rating Scale (BPRS)
Time frame: 16 weeks
Psychopathology - Clinical Global Impression (CGI)
Time frame: 16 weeks
Psychopathology - Global Assessment of Functioning (GAF)
Time frame: 16 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2026.
- 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.Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Margaret Hahn, PhD, MD principal investigator
Centre for Addiction and Mental Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Topiramate in people with Schizophrenia, Schizoaffective Disorder, run by Centre for Addiction and Mental Health at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 28 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Weight loss (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2026.