Adjunctive Methylphenidate ER in Patients With Schizophrenia to Improve Functional and Cognitive Outcomes

August 7, 2026 updated by: The Royal Ottawa Mental Health Centre

Adjunctive Methylphenidate Extended Release in Patients With Schizophrenia: a Single-centre Fixed Dose Cross-over Open-label Trial to Improve Functional and Cognitive Outcomes

Two of the major features of schizophrenia spectrum illness, negative and cognitive symptoms, have been associated with poor functional outcome and burden of illness. Given the proposed role of dopaminergic hypoactivity, augmentation with psychostimulants has been postulated as one of the potential treatment options for negative and/or cognitive symptoms of schizophrenia. The major drawback for use of these agents is a potential risk of relapse or worsening of psychosis through direct or indirect dopamine agonism activity and a great deal of caution has been called for use of stimulants in individuals with psychosis. However, preliminary results of earlier studies indicated improvement of negative and cognitive symptoms with off-label use of adjunctive psychostimulants. The present study aims to assess off-label use of adjunct psychostimulants in patients with schizophrenia in a tertiary mental health centre, focusing on efficacy and safety.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This project focuses on assessing efficacy of off-label use of adjunctive methylphenidate ER 36 mg among 24 stable patients with schizophrenia spectrum illness. This is a single centre study at the Royal Ottawa Mental Health Centre, Ottawa, Canada. An open-label fixed dose controlled cross-over trial is planned. Individuals (inpatients and outpatients) with schizophrenia who are stable on antipsychotic medications will be invited to participate in the study. Participants will be randomized into receiving four weeks of methylphenidate extended release (ER) 36 mg or treatment as usual and will switch group assignments for another 4 weeks. The duration of the study is 12 weeks for each participant, including 8 weeks of treatment (4 weeks treatment as usual and 4 weeks treatment as usual + adjunctive methylphenidate ER) and a follow-up visit at 12 weeks (study end point). A number of standardized scales will be used to measure functional capacity, cognition and symptom severity.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
35

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Canada
    • Ontario
      • Ottawa, Ontario, Canada, K1Z 7K4
        • Royal Ottawa Mental Health Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 51 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adult between the ages of 18-55; we chose an upper age limit of 55 years to exclude patients with potential age-related cognitive impairments which usually occur about a decade earlier in patients with schizophrenia
  • Inpatient or outpatient with schizophrenia spectrum illness, on any antipsychotic medication
  • Clinically stable for the past 4 weeks
  • Able to communicate in English

Exclusion Criteria:

  • Have known sensitivity to methylphenidate ER, as documented in the electronic medical record OR, as reported by the patient AND verified by pharmacy
  • Have had treatment with ECT in the past 6 months
  • Have a history of traumatic brain injury

  • Have a contraindication to psychostimulants including:

    1. Uncontrolled hypertension
    2. Significant cardiovascular abnormality including history of cardiac interventions, history of myocardial infarction, unstable arrhythmia, congenital heart disease
    3. Known family history of premature cardiac death (for males <45, females <55)
    4. Known history of glaucoma
  • Are currently pregnant or planning to become pregnant- a rapid urine pregnancy test will be done for female participants, and a refusal to take the test or a positive test will exclude the participant
  • Have a diagnosis of substance induced psychosis
  • Have any of the following diagnoses: neurodevelopmental delay, intellectual disability or neurocognitive disorder (dementia)
  • Have a diagnosis of another currently significant and unstable psychiatric condition (i.e. depressive episode, active substance use disorder, etc.)
  • Have a history of previous safety concerns directly driven by positive symptoms (e.g history of suicide attempt as directed by auditory hallucinations)
  • Have current active suicidality

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Apo-Methylphenidate ER arm
Apo-Methylphenidate ER, 36 mg, oral, once a day, every morning, 4 weeks duration. Methylphenidate ER will be started at 18 mg to test tolerability and will be titrated at day 7 to a dose of 36 mg.
Drug: Apo-Methylphenidate ER
For inpatients, the study medication will be administered by unit nurses, alongside their other medications. For outpatients, the study medication will be dispensed to the participant by the research assistant during their weekly visit. Patients will continue their regular medications as per standard of care.
No Intervention: Treatment as usual arm
Participants in the treatment as usual arm will continue with their current treatment as decided by their treatment team.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Defined as change in functioning
Time Frame: VRFCAT will be implemented at baseline, week 4, 8 and at follow-up at week 12.
Change in functioning will be measured using the Virtual Reality Functional Capacity Assessment (VRFCAT) tool. The VRCAT is an interactive computerized measure of functional capacity. It presents the user with real life scenarios such as shopping, taking a bus, completing a recipe, etc, and assesses key instrumental activities of daily living in a realistic and interactive virtual environment.
VRFCAT will be implemented at baseline, week 4, 8 and at follow-up at week 12.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Defined as change in cognitive functioning (domains include verbal memory, working memory, motor speed, attention and processing speed, verbal fluency and executive functioning)
Time Frame: BACS will be implemented at baseline, week 4, 8 and at follow-up at week 12.
Change in cognitive functioning will be measured using the Brief Assessment of Cognition in Schizophrenia (BACS). The BACS is a tool to assess aspects of cognition found to be the most impaired and correlated with outcome in patients with schizophrenia. It consists of six domains: verbal memory, working memory, motor speed, attention and processing speed, verbal fluency and executive functioning.
BACS will be implemented at baseline, week 4, 8 and at follow-up at week 12.

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Defined as symptom severity (items include delusions, conceptual disorganization, hallucinations, blunted affect, social withdrawal, lack of spontaneity/flow of conversation)
Time Frame: The PANSS-6 will be completed at all time points (baseline, weeks 1-8, and at follow-up at week 12.
Symptom severity will be measured using the Positive and Negative Syndrome Scale 6-item (PANSS-6). The PANSS-6 is a 6-item version of the PANSS scale, and includes P1 = delusions, P2 = conceptual disorganization, P3 = hallucinations, N1 = blunted affect, N4 = social withdrawal, N6 = lack of spontaneity/flow of conversation. Items are rated on a 7-point scale from 1(absent) to 7(extreme), with a total range of 6-42, with higher scores indicative of more severe symptoms. The PANSS-6 has been shown to adequately measure severity, remission, and antipsychotic efficacy related to core positive and negative symptoms in clinical trials and its validity and sensitivity have been demonstrated in treatment resistant schizophrenia.
The PANSS-6 will be completed at all time points (baseline, weeks 1-8, and at follow-up at week 12.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
The Royal Ottawa Mental Health Centre

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Naista Zhand, M.D., Royal Ottawa Mental Health Centre

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 9, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 21, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 18, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 7, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 7, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 10, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 12, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 7, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2021025

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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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