Effect of Methylphenidate on Cancer-related Cognitive Impairment

Study Overview
=================
Brief Summary
-----------------
Cancer-related cognitive Impairment (CRCI), commonly referred to as chemo brain or brain fog-impact severely on the Quality of Life (QoL) of cancer survivors. However, it still remains underdiagnosed and challenging to treat. One of the treatment options is the use of psychostimulants such as Methylphenidate (MP), but well-designed clinical trials to test its efficacy are limited. We will conduct a phase II study with a mixed method design to explore the preliminary efficacy of MP to improve cognitive function and QoL in breast cancer patients after treatment with chemotherapy and/or radiotherapy and determine the parameters needed for designing a phase III study.

Detailed Description
-----------------
Objectives: The main objective of this study is to determine the parameters for a phase III study to measure the efficacy of MP in improving CRCI in women with breast cancer who received chemotherapy and/or radiotherapy. In addition, the profile of drug side effects will be estimated. A better understanding of CRCI and its impact on the activities and QoL of the study population is targeted. Population: The sample will consist of 40 women in remission of non-metastatic breast cancer whose profile meets the following criteria: receiving follow-up at the radio-oncology department of the CHU de Québec-Université Laval or at any other health institutions in Quebec participating in the project; complaining about cognitive impairment; not having any contraindications to the taking of MP or any medical condition that may interfere with his taking and/or any medical condition that could explain the cognitive impairment. Before study inclusion, the eligibility of these women will be validated by questionnaires and medical records. Study design: This study will follow the design of a randomized, double-blind, placebo-controlled trial that includes a mixed methodology (convergent design). Procedures: The study will be divided into two phases. The first phase will start at time T0, before any MP is taken, and will last 14 days (T1). Participants will be assigned to the intervention group, where they will receive 10 mg of MP controlled-release (SR) for 14 days, or the control group where they will receive an identical placebo capsule for 14 days. The second phase begins at T1 and ends 14 days later (T2). This phase will explore a higher dosage. Participants from the intervention group during phase 1 will received an increased dose of MP (20 mg - two capsules) during 14 days whereas participants from the control group will receive two placebo capsules during 14 days. Measures: Quantitative data. Questionnaires and tests will be used. The effect size calculation will be based on the 'Perceived Cognitive Impairments' (PCI) subscale of the Functional Assessment of Cancer Therapy-Cognitive Function questionnaire (FACT-Cog) test and will be used to determine the required power for a phase III study. Other tests will be explored to assess the sensitivity to measure cognitive changes. Descriptive statistical analysis will be performed. Tests such as the T-Test, χ2 and ANOVA will be used to estimate the degree of improvement of cognitive function by comparing data of the different groups. Qualitative data. Interviews will be conducted with the 40 women included in the study. These interviews will focus on their experience of cognitive deficits before and after taking MP/Placebo at T0 and T2. In order to document the experience of these women and to assess the transferability of the resutls, two methods will be combined to analyze these interviews: an intra-case analysis and an inter-case analysis. Each of the components of the study will answer its main questions independently. However, the data will also be matched (triangulation) to provide a global understanding of the issue and convergence of results when possible.

Official Title
-----------------
Étude Pilote de Phase II Sur l'Effet du méthylphénidate Sur la Fonction Cognitive Des Patientes en rémission d'un Cancer du Sein

Conditions
-----------------
Breast Cancer Female, Cancer-Related Condition

Intervention / Treatment
-----------------
* Drug: Methylphenidate HCl 10Mg SR
* Drug: Placebo Group


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Breast cancer stage I, II or III Completed chemotherapy and/or radiotherapy at least 6 months before entering the study Being in remission of breast cancer Complaining of cognitive impairment Exclusion Criteria: Current or recent use (<2 years) of psychostimulant drugs Women receiving drugs with a potential of interaction with methylphenidate: i. Anticoagulants; ii. Antidepressants with the exception of: amitriptyline (≤75mg); citalopram (≤40mg); desipramine (≤75mg); duloxetine (≤60mg); escitalopram (≤20mg); fluoxetine (≤60mg); fluvoxamine (≤150mg); mirtazapine (≤60mg); nortriptyline (≤50mg); trazadone (≤50mg); venlafaxine (≤150mg); vortioxetine (≤20mg); iii. Drugs (cocaine); iv. Erythropoietin; v. Drugs acting on the cerebral dopaminergic system, including drugs that inhibit monoamine oxidase; vi. John's wort, natural medicines for depression or supplements for fatigue. Conditions that may increase the risk of cognitive impairment or toxicity of methylphenidate such as: i. Pregnancy and breastfeeding ii. Bipolar status iii. Cerebral tumor or any brain injury iv. Metastatic cancer v. Alcohol addiction vi. Active Major depression vii. Parkinson disease viii. Dementia ix. Epilepsia x. Glaucoma xi. Cardiovascular diseases xii. Auto-immunes and chronic inflammatory disease xiii. Cerebrovascular disease xiv. Narcolepsy xv. Pheochromocytoma xvi. Thyrotoxicosis xvii. Motor tic, Tourette syndrome xviii. Generalized anxiety disorder or panic attacks xix. Living under the same roof as people taking Biphentin® 10 mg capsules (this exclusion criteria is necessary because the placebo capsule is identical to the commercial formulation of Biphentin®) xx. Any other medical criteria, according to the clinical judgment of the principal investigator.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Methylphenidate HCl 10Mg SR<br>Participants of the intervention group (n=20) will receive 1 capsule of Methylphenidate HCl 10 mg SR each morning during 14 days during phase 1 and 2 capsules of Methylphenidate HCl 10 mg SR each morning during 14 days during phase 2. | Drug: Methylphenidate HCl 10Mg SR<br>* Methylphenidate HCl 10Mg SR (Phase 1) and Methylphenidate HCl 20Mg SR (Phase 2)<br>|
| Placebo Comparator: Placebo Group<br>Participants of the control group (n=20) will receive 1 capsule of placebo each morning during 14 days during phase 1 and 2 capsules of placebo each morning during 14 days during phase 2. | Drug: Placebo Group<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cognitive impairment level | 'Perceived Cognitive Impairments' (PCI) subscale of the Functional Assessment of Cancer Therapy-Cognitive Function questionnaire (FACT-Cog) test | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Methylphenidate side effects | Tracking and registration of methylphenidate side effects | Up to 24 months | 
| Methylphenidate effect on fatigue | Fatigue evaluation with a validated questionnaire: Multidimensional Fatigue Inventory (MFI) | Up to 24 months | 
| Experience of women with cancer-related cognitive impairment in cancer | Semi-structured interviews | Up to 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cognitive impairment, Methylphenidate, Cancer-related cognitive impairment, Mixed method, Phase II study, Breast cancer