- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04478838
"Extended" (Alternate Day) Antipsychotic Dosing
"Re-examining Maintenance Antipsychotic Treatment in Schizophrenia: "Extended" Antipsychotic Dosing"
The study wishes to examine whether "extended" antipsychotic treatment, in this case, antipsychotic treatment every other day, is as effective as daily treatment. It is also evaluating whether there may be differences in terms of side effects.
Participants will be randomly assigned to either the treatment as usual group (i.e., taking antipsychotic daily) or the extended dosing group (i.e., taking antipsychotic one day on, one day off). That means, like flipping a coin, there is a 50/50 chance that participants will continue on daily dosing of your antipsychotic or have it switched to every other day dosing.
This study will last for 1 year. Participants will be evaluated at the beginning and every two weeks during the first 6 months, with visits once every 4 weeks for the final 6 months. In total, participants will make 22 visits over 52 weeks to the investigator's office.
The investigators hypothesize that with ED, there will be no change in symptom severity but improvement in the frequency and severity of side effects, wellbeing, and functioning.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a randomized, double-blind, controlled trial that will compare ED, i.e. alternate day dosing to daily dosing i.e. TAU.
Individuals will be randomized to ED or TAU using a permuted block design with a random number generator. The size will be fixed and study personnel blinded to the randomization block size.
To maintain a double-blind design, our pharmacy will provide, on an individualized basis, APs at the appropriate dose and placebo where necessary in matching gelatin capsules, packaged in blister packs. The active tablet will be over-encapsulated, and matching placebo will be prepared using the same capsules (filled with lactose). Thus, from the individual subject's position, AP treatment is continued according to the same daily schedule. Further, if their current medication is prescribed in divided doses, this too will be employed during the study. The minimum and maximum doses for Risperidone will be 1 mg and 16mg respectively. The minimum and maximum doses for Olanzapine will be 5 mg and 20mg respectively. Other psychotropic medications prescribed before the study will be permitted, with any changes in dosing during its course documented
The trial is 1 year in duration. To prevent bias, the study code will remain blinded until the trial's completion.
Study visits will be scheduled every 2 weeks over the first 6 months, in line with the earlier investigation. Thereafter, the visits will be decreased to every 4 weeks, aligning with the schedule routinely observed in our ambulatory clinics.
The investigators are asking the following questions:
- (Non-inferiority) Can additional confirmatory evidence support "extended" AP dosing (ED) as an alternative to continuous administration, i.e. is it as effective clinically?
- (Superiority) Can the investigators establish clinical benefits (e.g. better tolerability, fewer side effects, such as decreased glucose dysregulation) with ED?
Hypothesis: The investigators hypothesize that with ED, there will be no change in symptom severity but improvement in the frequency and severity of side effects, wellbeing, and functioning.
Study Type
Enrollment (Estimated)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Carol Borlido
- Phone Number: 30547 416-535-8501
- Email: carol.borlido@camh.ca
Study Contact Backup
- Name: Gary Remington, MD, PhD
- Phone Number: 34750 416-535-8501
- Email: gary.remington@camh.ca
Study Locations
-
-
Ontario
-
Toronto, Ontario, Canada, M5T 1R8
- Recruiting
- Centre for Addiction and Mental Health
-
Principal Investigator:
- Gary J Remington, MD, PhD
-
Contact:
- Gary J Remington, MD, PhD
- Phone Number: 34750 416-535-8501
- Email: gary.remington@camh.ca
-
Contact:
- Carol Borlido
- Phone Number: 34321 416-535-8501
- Email: caro.borlido@camh.ca
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
(i) A primary diagnosis of a Schizophrenia Spectrum or Other Psychotic Disorder as defined by the DSM-5 diagnosis and confirmed by the MINI (Version 7.0.2)
(ii) age 18 or older
(iii) female participants of childbearing potential must be using a reliable method of contraception and have a negative pregnancy test at the time of enrolment and must, in the investigator's opinion, practice a clinically accepted, reliable method of contraception during this study. Male participants must not father a baby during their time in the study
(iv) ability to communicate in English
(v) capacity to provide written, informed consent, as assessed using the MacCAT-CR at time of consent
(vi) stabilized as outpatients with a single oral AP (risperidone or olanzapine*) at the same dose for ≥3 months i. On a prescribed risperidone dose of between 1-6mg, or a prescribed olanzapine dose of between 5-20mg
(vii) evidence of adherence with current AP treatment
Exclusion Criteria:
(i) exposure to a depot AP within 1 year (i.e., no depot AP injection within the last year)
(ii) Current diagnosis of substance use disorder according to DSM-5 criteria (verified through the MINI for Psychotic Disorders (Version 7.0.2) and a positive drug screen for street and /or prescription drugs not prescribed to the participant by treating physicians
(iii) ECT within the last 3 months
(iv) pregnancy or lactation
(v) neurological condition (dementia including Alzheimer's disease, multiple sclerosis, epilepsy, stroke, or traumatic brain injury)
(vi) allergy to the study drugs and their excipients
(vii) allergy or intolerance to lactose
(viii) negative urine drug screen result for Olanzapine or Risperidone
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Extended Dosing Group
Participants taking olanzapine or risperidone will be switched to an alternate day dosing schedule.
|
0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg and 4 mg Tablets
Other Names:
2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg Tablets
Other Names:
|
No Intervention: Treatment as Usual group
Participants will continue to take their olanzapine or risperidone following the same prescribed daily schedule.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical Deterioration using the "Brief Psychiatric Rating Scale - Expanded"
Time Frame: 0 and 52 weeks
|
Change in the Brief Psychiatric Rating Scale - total scores from baseline to 52 weeks. The score values for each item on the BPRS range from 1 to 7. The higher the score for each item the worse the outcome. The values for each item on the BPRS are scored as follows: 1- Not Present, 2 - Very Mild, 3- Mild, 4- Moderate, 5 - Moderately Severe, 6- Severe, 7- Very Severe. |
0 and 52 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Exploratory Outcomes - Symptoms 1 using "The Clinical Global Impression - Schizophrenia Scale"
Time Frame: 0 and 52 weeks
|
Change in Clinical Global Impression - Schizophrenia (CGI-SCH) severity of illness scores from baseline to 52 weeks. The severity of illness score values for each item on the CGI- SCH range from 1 to 7. The higher the score for each item the worse the outcome. The severity of illness values are scored as follows: 1- Normal, not ill, 2 -Minimally ill, 3- Mildly ill, 4- Moderately ill, 5 - Markedly ill, 6- Severely ill, 7- Among the most severely ill. |
0 and 52 weeks
|
Exploratory Outcomes - Symptoms/Side Effects using "The Clinical Global Impression - Schizophrenia Scale"
Time Frame: 0 and 52 weeks
|
Change in Clinical Global Impression - Schizophrenia Scale (CGI-SCH) degree of change scores from baseline to 52. The values range from 1-7. The higher the score for each item the worse the outcome. The score value of each item are as follows: 1 - Very much improved, 2 - Much Improved, 3 - Minimally improved, 4 - No Change, 5 - Minimally Worse, 6- Much Worse, 7 - Very Much Worse |
0 and 52 weeks
|
Exploratory Outcomes - Symptoms 3 using the "Calgary Depression Scale for Schizophrenia"
Time Frame: 0 and 52 weeks
|
Change in Calgary Depression Scale (CDS) scores from baseline to 52 weeks.
Scores range from 0-3 as follows: 0- Absent, 1- Mild, 2- Moderate, 3 - Severe.
The higher the score for each item, the worse the outcome.
|
0 and 52 weeks
|
Exploratory Outcomes - Symptoms 4 using the "Yale-Brown Obsessive-Compulsive Scale"
Time Frame: 0 and 52 weeks
|
Change in Yale-Brown Obsessive-Compulsive Scale (YBOCS) scores from baseline to 52 weeks.
Scores range from 0-4 with higher scores indicating worsening of outcome.
|
0 and 52 weeks
|
Exploratory Outcomes - Symptoms 5 using the "Hamilton Anxiety Scale"
Time Frame: 0 and 52 weeks
|
Change in Hamilton Anxiety Scale (HAM-A) scores from baseline to 52 weeks.
Scores on each item range from 0-4 as follows: 0- not present, 1- mild, 2 - moderate, 3- severe, 4 - very severe.
Higher scores on each item and total score indicate worsening of anxiety outcome.
|
0 and 52 weeks
|
Exploratory Outcomes - Side Effects 1 using the "Leibowitz Social Anxiety Scale"
Time Frame: 0 and 52 weeks
|
Change in Liebowitz Social Anxiety Scale (LSAS) scores from baseline to 52 weeks.
For each item, there are 2 scores; 1) score for fear of anxiety and 2) score for avoidance.
For the fear of anxiety component of the scale, score ranges from 0-3 as follows: 0- None, 1- Mild, 2- Moderate, 3 - Severe.
The scores for the Avoidance component of the scale ranges from 0-3 as follows: 0 - Never, 1- Occasionally, 2 - Often, 3 - Usually.
The higher the score the worse the outcome.
|
0 and 52 weeks
|
Exploratory Outcomes - Side Effects 3 using the "Glasgow Assessment Side-Effect Scale"
Time Frame: 0 and 52 weeks
|
Change in Glasgow Assessment Side-Effect Scale (GASS) scores from baseline to 52 weeks.
Scores range from 0-3 as follows: 0 -Never, 1- Once, 2 - A few times, 3 - Everyday.
The higher the score for each item and higher total indicates a worse side effect outcome.
|
0 and 52 weeks
|
Exploratory Outcomes - Side Effects 4 using the "Drug Attitude Inventory" Scale
Time Frame: 0 and 52 weeks
|
Change in Drug Attitude Inventory (DAI) scores from baseline to 52 weeks.
Scores are based on 30 true/false statements.There are 15 items that a patient who is fully adherent to their prescribed medication (and so would be expected to have a positive response to medication would answer true and 15 items such a patient would answer as false.
Each positive answer is given a score of plus one, and each negative answer is given a score of minus one.
The total positive score would indicate a positive response (adherent to medication) whereas a negative total score would indicate a negative response (non adherent to medication).
|
0 and 52 weeks
|
Exploratory Outcomes - Side Effects 5 using the "Barnes Akathisia Rating Scale"
Time Frame: 0 and 52 weeks
|
Change in Barnes Akathisia Rating Scale (BARS) scores from baseline to 52 weeks.
The total score for the global clinical assessment of akathisia ranges from 0-5 with higher score indicating a worsening of akathisia.
|
0 and 52 weeks
|
Exploratory Outcomes - Side Effects 6 using the "Simpson Angus Scale"
Time Frame: 0 and 52 weeks
|
Change in Simpson Angus Scale (SAS) scores from baseline to 52 weeks.
There are 13 items in the scale; scores on each item range from 0-4 with higher scores indicating worse extrapyramidal outcome.
|
0 and 52 weeks
|
Exploratory Outcomes - Side Effects 7 using the "Abnormal Involuntary Movement Scale"
Time Frame: 0 and 52 weeks
|
Change in Abnormal Involuntary Movement Scale (AIMS) scores from baseline to 52 weeks.
There are 13 items in the scale, scores on each item range from 0-4 with higher scores indicating a worse outcome in abnormal movements.
|
0 and 52 weeks
|
Exploratory Outcomes - Wellbeing using the "Quality of Life and Satisfaction Questionnaire"
Time Frame: 0 and 52 weeks
|
Change in Quality of Life Scale (QLS) scores from baseline to 52 weeks.
The scores for each item range from 0-6.
The higher the score, the better the outcome.
On several items, there is an additional score of "9" to indicate "not applicable".
|
0 and 52 weeks
|
Exploratory Outcomes - Wellbeing 2 using the "Quality of Life and Satisfaction Questionnaire - Short Form"
Time Frame: 0 and 52 weeks
|
Change in Quality of Life and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) scores from baseline to 52 weeks.
Scores range from 0-6 with lower scores indicating a worse outcome.
|
0 and 52 weeks
|
Exploratory Outcomes - Wellbeing 3 using the "Subject Happiness Scale"
Time Frame: 0 and 52 weeks
|
.Change in Subjective Happiness Scale (SHS) scores from baseline to 52 weeks.
There are 4 items; scores on each item range from 1-7 with higher scores indicating a happier outcome.
|
0 and 52 weeks
|
Exploratory Outcomes - Function 1 using the "Social and Occupational Function Assessment Scale"
Time Frame: 0 and 52 weeks
|
Change in : Social and Occupational Function Assessment Scale (SOFAS).
scores from baseline to 52 weeks.
A total score ranges from 0-100 with higher scores indicating better social and occupational functioning..
|
0 and 52 weeks
|
Exploratory Outcomes - Function 2 using the "Personal and Social Performance Scale"
Time Frame: 0 and 52 weeks
|
Change in Personal and Social Performance scale (PSP) scores from baseline to 52 weeks.
The ratings are based on four areas (a) socially useful activities, including work and study; b) personal and social relationships; c) self, and d) disturbing and aggressive behaviours.
Overall score range from 1-100.
The higher the overall rating, the better the outcome.
The breakdown of the total Rating score are as follows: scores ranging from 1-30 reflect functioning so poor that intensive support or supervision is needed; ratings from 31-70 reflect manifest disabilities of various degrees; ratings from 71-100 reflect only mild difficulties.
|
0 and 52 weeks
|
Exploratory Outcomes - Function 3 using the "Recovery Assessment Scale"
Time Frame: 0 and 52 weeks
|
Change in Recovery Assessment Scale (RAS) scores from baseline to 52 weeks.
There are 41 items with scores on each item ranging from 1-5 with higher scores indicating better outcomes.
|
0 and 52 weeks
|
Exploratory Outcomes - Side Effects 2 using the "Neurological Evaluation Scale"
Time Frame: 0 and 52 weeks
|
Change in Neurological Evaluation Scale (NES) scores from baseline to 52 weeks.
There are 12 items and scores for each item range from 0-2 with higher scores indicating worsening of outcome.
Item 5 does not require a score.
|
0 and 52 weeks
|
Collaborators and Investigators
Investigators
- Principal Investigator: Gary J Remington, MD, PhD, Centre for Addiction and Mental Health
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Schizophrenia Spectrum and Other Psychotic Disorders
- Schizophrenia
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Autonomic Agents
- Peripheral Nervous System Agents
- Antiemetics
- Gastrointestinal Agents
- Antipsychotic Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Serotonin Agents
- Dopamine Agents
- Serotonin Antagonists
- Dopamine Antagonists
- Selective Serotonin Reuptake Inhibitors
- Olanzapine
- Risperidone
Other Study ID Numbers
- 154-2018
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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