Clinical trial NCT05414058: 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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Schizophrenia Schizoaffective
Keywords: schizophrenia
methylphenidate
functional outcomes
Lead sponsor: The Royal Ottawa Mental Health Centre
Sponsor class: OTHER
First posted: 2022-06-10
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: TREATMENT

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 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.

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
* 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

Primary outcomes:
measure: Defined as change in functioning
timeFrame: VRFCAT will be implemented at baseline, week 4, 8 and at follow-up at week 12.
Secondary outcomes:
measure: Defined as change in cognitive functioning (domains include verbal memory, working memory, motor speed, attention and processing speed, verbal fluency and executive functioning)
timeFrame: BACS will be implemented at baseline, week 4, 8 and at follow-up at week 12.
Other outcomes:
measure: Defined as symptom severity (items include delusions, conceptual disorganization, hallucinations, blunted affect, social withdrawal, lack of spontaneity/flow of conversation)
timeFrame: The PANSS-6 will be completed at all time points (baseline, weeks 1-8, and at follow-up at week 12.
Locations:
city: Ottawa
country: Canada
facility: Royal Ottawa Mental Health Centre
state: Ontario
Study officials:
affiliation: Royal Ottawa Mental Health Centre
name: Naista Zhand, M.D.
role: PRINCIPAL_INVESTIGATOR
References: