Effect of Methylphenidate on Cancer-related Cognitive Impairment

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

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, 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 Quality of life in breast cancer patients after treatment with chemotherapy and/or radiation therapy and determine the parameters needed for designing a phase III study. This study will include two phases: Phase one: randomized placebo-controlled clinical trial, phase 2 open-label trial.

Trial Description

Primary Outcome:

  • Change in cognitive impairment level
Secondary Outcome:
  • Methylphenidate side effects
  • Methylphenidate effect on fatigue
  • Experience of women with Cancer-related Cognitive Impairment in cancer

Objectives: The main objective of this study is to determine the parameters for a Phase III study to measure the efficacy of methylphenidate (MP) in improving cognitive deficits in women with Breast cancer who had received chemotherapy and / or radiotherapy. In addition, the profile of drug side effects will be estimated. A better understanding of Cancer-related cognitive impairment and its impact on the activities and quality of life of the study population will be targeted.

Population: The sample will consist of 40 women in remission from non-metastatic breast cancer, with follow-up at the Department of Radio-Oncology, CHU de Québec-Université Laval-L'Hôtel-Dieu de Québec, who had received chemotherapy or radiotherapy, complaining of cognitive impairment, and without any medical condition or contraindications to MP that may interfere with the drug or the cognitive impairment status. Before study inclusion, the eligibility of these women will be validated by questionnaires and verification of their medical records.

Recruitment: Recruitment will be made with the help of the radio-oncology team who will refer patients to the research team. As alternative recruitment method, we will use posters. flyers and advertisement. Finally, recruitment could be made through the clinical trial.gov website.

Study design: A mixed methodology with a convergent design will be used in this pilot clinical trial.

Procedures:

The study quantitative component will use questionnaires and tests assessing cognitive function in order to estimate the effect size to be used in the design of a Phase III clinical trial and will be divided into two phases. The first phase corresponds to a double-blind randomized placebo-controlled trial which will test the effect of MP on cognitive function. This phase begins at time T0, before any MP is taken, and ends 14 days after, T1. Participants will be assigned randomly to the intervention, where they will receive 10 mg of methylphenidate (Biphentin, slow released) for 14 days or control group where they will receive placebo.

The second phase is an open-label study that will explore a higher dosage. In this phase, all participants will receive methylphenidate SR at an increasing dose starting at 10 mg for a week (1capsule). After evaluation, this dosage will be increased, if possible, to 20 mg per day (2 capsules).

Depending on their response to the starting dose of MP, for the following 7 days, they will receive:

  • no Methylphenidate (no capsule), if they have important side effect;
  • Methylphenidate 10 mg (1 capsule) if they have sufficient improvement or do not want to increase the dosage
  • Methylphenidate 20 mg (2 capsules) if they have partial or no improvement without important side-effects. This phase begins at the end of the first phase T1 and ends 14 days after, T2.

Measures: The calculation of the effect size will be based on the Auditory consonant trigrams which will be used to determine the power required for a Phase III study. This test will also be used to test the sensitivity of the Fast Cognitive Evaluation tool (FaCE) which is a new test developed and validated by our team.

The global change in cognitive function will also be evaluated by the (FaCE). Other tests will be explored to assess their sensitivity in measuring cognitive changes.

Here is the list of measures: Rotterdam Checklist Symptom, Unipedal Balance Test, Stroop test, The Functional Assessment of Cancer Therapy-Cognitive Function, Multidimensional fatigue inventory, Distress Thermometer.

Analysis: Descriptive statistical analyses will be carried out. Using tests such as T-test, χ2 and ANOVA we will also estimate the degree of improvement in cognitive function by comparing data from the Placebo and the methylphenidate group.

The qualitative component will explore, through a 1-hour individual interview with the 40 women included in the study, their experience of cognitive deficits before and after MP / placebo, at T0 and T1. The analysis of these interviews will be carried out by combining two methods: an intra-case analysis and an inter-case analysis, in order to properly document the experience of these women and to arrive at an assessment of the transferability of the results.

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 where possible.

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society