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

Schizophrenia Schizoaffective Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05414058
• Other study ID #: 2021025
• Status: Recruiting
• Phase: Phase 2
• Start date: September 9, 2022
• Est. completion date: September 9, 2025

Study information

• Verified date: March 2024
• Source: The Royal Ottawa Mental Health Centre
• Contact: Carrie Robertson
• Phone: 613 722-6521
• Email: carrie.robertson[@]theroyal.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: September 9, 2025
• Est. primary completion date: September 9, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Schizophrenia
• Schizophrenia Schizoaffective

Intervention

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.

Locations

Country	Name	City	State
Canada	Royal Ottawa Mental Health Centre	Ottawa	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
The Royal Ottawa Mental Health Centre

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Defined as symptom severity (items include delusions, conceptual disorganization, hallucinations, blunted affect, social withdrawal, lack of spontaneity/flow of conversation)	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.
Primary	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	Defined as change in cognitive functioning (domains include verbal memory, working memory, motor speed, attention and processing speed, verbal fluency and executive functioning)	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.