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

Primary Purpose

Schizophrenia Schizoaffective

Status

Recruiting

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

Apo-Methylphenidate ER

About this trial

This is an interventional treatment trial for Schizophrenia Schizoaffective focused on measuring schizophrenia, methylphenidate, functional outcomes

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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
Patients with schizophrenia spectrum illness, on any antipsychotic medication
Clinically stable for the past 8 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 head injury resulting in loss of consciousness
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, learning disorder 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

Sites / Locations

Royal Ottawa Mental Health CentreRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Apo-Methylphenidate ER arm

Treatment as usual arm

Arm Description

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.

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

Outcomes

Primary Outcome Measures

Defined as improvement in functioning

Improvement 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.

Secondary Outcome Measures

Defined as improvement in cognitive functioning

Improvement 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.

Full Information

NCT ID

NCT05414058

First Posted

June 7, 2022

Last Updated

October 31, 2022

Sponsor

The Royal Ottawa Mental Health Centre

1. Study Identification

Unique Protocol Identification Number

NCT05414058

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Recruiting

Study Start Date

September 9, 2022 (Actual)

Primary Completion Date

September 9, 2025 (Anticipated)

Study Completion Date

September 9, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

The Royal Ottawa Mental Health Centre

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

This project focuses on assessing efficacy of off-label use of adjunctive methylphenidate ER 36 mg among 24 stable inpatients 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Schizophrenia Schizoaffective

Keywords

schizophrenia, methylphenidate, functional outcomes

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Model Description

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.

Masking

None (Open Label)

Masking Description

An open-label fixed dose controlled cross-over trial is planned.

Allocation

Randomized

Enrollment

24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Apo-Methylphenidate ER arm

Arm Type

Experimental

Arm Description

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.

Arm Title

Treatment as usual arm

Arm Type

No Intervention

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Apo-Methylphenidate ER

Intervention Description

The study medication will be administered by a clinical registered nurse (RN), alongside their other medications. Patients will continue their regular medications as per standard of care.

Primary Outcome Measure Information:

Title

Defined as improvement in functioning

Description

Time Frame

VRFCAT will be implemented at baseline, week 4, 8 and at follow-up at week 12.

Secondary Outcome Measure Information:

Title

Defined as improvement in cognitive functioning

Description

Time Frame

BACS will be implemented at baseline, week 4, 8 and at follow-up at week 12.

Other Pre-specified Outcome Measures:

Title

Defined as symptom severity

Description

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. 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.

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

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 Patients with schizophrenia spectrum illness, on any antipsychotic medication Clinically stable for the past 8 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 head injury resulting in loss of consciousness 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, learning disorder 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Carrie Robertson

Phone

613 722-6521

Ext

6745

carrie.robertson@theroyal.ca

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Naista Zhand, M.D.

Organizational Affiliation

Royal Ottawa Mental Health Centre

Official's Role

Principal Investigator

Facility Information:

Facility Name

Royal Ottawa Mental Health Centre

City

Ottawa

State/Province

Ontario

ZIP/Postal Code

K1Z 7K4

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Naista Zhand, MD

Phone

613722-6521

Ext

6780

naista.zhand@theroyal.ca

First Name & Middle Initial & Last Name & Degree

Carrie Robertson, BA

Phone

613722-6521

Ext

6745

carrie.robertson@theroyal.ca

First Name & Middle Initial & Last Name & Degree

Naista Zhand, MD

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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