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

NCT05414058 | Completed Phase 2 DMC

• 1 other identifier: 2021025
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Schizophrenia Schizoaffective

Keywords

schizophrenia; methylphenidate; functional outcomes

Outcome Measures

Primary Outcomes (1)

• Defined as change in functioning

  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 Outcomes (1)

• Defined as change in cognitive functioning (domains include 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 Outcomes (1)

• Defined as symptom severity (items include delusions, conceptual disorganization, hallucinations, blunted affect, social withdrawal, lack of spontaneity/flow of conversation)

  The PANSS-6 will be completed at all time points (baseline, weeks 1-8, and at follow-up at week 12.

Study Arms (2)

Apo-Methylphenidate ER arm

EXPERIMENTAL

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

Treatment as usual arm

NO INTERVENTION

Participants in the treatment as usual arm will continue with their current treatment as decided by their treatment team.

Interventions

Apo-Methylphenidate ER DRUG

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.

Apo-Methylphenidate ER arm

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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:
• Uncontrolled hypertension
• Significant cardiovascular abnormality including history of cardiac interventions, history of myocardial infarction, unstable arrhythmia, congenital heart disease
• Known family history of premature cardiac death (for males \<45, females \<55)
• 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

Sponsors & Collaborators

• The Royal Ottawa Mental Health Centre: lead

Study Sites (1)

Royal Ottawa Mental Health Centre

Ottawa, Ontario, K1Z 7K4, Canada

Location

MeSH Terms

Conditions

Psychotic Disorders; Schizophrenia

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Officials

• Naista Zhand, M.D.

  Royal Ottawa Mental Health Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: An open-label fixed dose controlled cross-over trial is planned.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: An open-label fixed dose controlled cross-over trial is planned. Participants will be randomized into one of two arms: 1) participants will receive four weeks of add-on methylphenidate ER 36 mg, or 2) participants will receive 4 weeks of treatment as usual (no-treatment control group). At 4 weeks, participants will switch arms for another 4 weeks.

Study Record Dates

• First Submitted: June 7, 2022
• First Posted: June 10, 2022
• Study Start: September 9, 2022
• Primary Completion: August 21, 2024
• Study Completion: September 18, 2024
• Last Updated: December 12, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)