MODIFY: Modafinil to Improve Fatiguability

Sponsor

Ottawa Hospital Research Institute (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05333250

Collaborator

The Ottawa Hospital (Other), Bruyere Research Institute (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

3.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Cancer-related fatigue (CRF) and cancer-related cognitive impairment (CRCI) are among the most commonly reported disabling symptoms experienced by patients with advanced cancer. However, there are currently limited evidence-based pharmacologic interventions available. The investigators will conduct a Vanguard Randomized Clinical Trial (RCT) to estimate the effect of modafinil in managing CRF and CRCI, and to test the feasibility of carrying out the study.

Condition or Disease	Intervention/Treatment	Phase
Cancer-related Cognitive Difficulties Cancer-related Problem/Condition Fatigue	Drug: Modafinil Other: Placebo	Phase 3

Detailed Description

Background:

Patients with advanced cancer often experience various disabling symptoms. Cancer-related fatigue (CRF) and cancer-related cognitive impairment (CRCI) are among the most common reported symptoms, yet the availability of evidence-based pharmacologic interventions is limited.

CRF can be defined as a "distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning." CRF is experienced by over 75% of patients with advanced cancer.

CRCI is defined as a decline in one or more areas of cognitive function, including attention and concentration, executive functioning, information processing speed, language, visuospatial skill, psychomotor ability, and memory. It is estimated that up to 40% of patients experience CRCI prior to any treatment; up to 75% during their treatment; and up to 60% upon completion of therapies.

Modafinil is a psychostimulant that has been studied in the context of CRF and daytime sleepiness. Its mechanism of action is not clear, but it is thought to promote wakefulness through dopaminergic neurotransmission which has been hypothesized to play a role in CRF.

Study Hypothesis:

Modafinil will improve CRF and CRCI

Study Objectives:

To estimate the effect size of modafinil in managing CRF and CRCI
To test the feasibility of carrying out the study (recruitment, etc.)

Study Design:

Randomized, placebo-controlled, double-blind, single-centre vanguard trial

Sample Size & Study Population:

Approximately 40 outpatients presenting ≥4/10 on the fatigue score of their screening questionnaire will be recruited. Eligible patients must be 18-75 years old with advanced cancer who have not received cytotoxic chemotherapy for at least one month.

Intervention:

Subjects will be randomized to receive 200 mg of modafinil or placebo once daily for one week.

Study Outcome Measures:

Using validated questionnaires and a digital tool, the investigators will assess the patient's fatigue (CRF), cognition (CRCI), and quality of life before and after the intervention. In addition, patients will report their global impression of change.

Finally, if patients experience any adverse events (headache, nausea, vomiting, anxiety, etc.), they will report them using a standard questionnaire. Adverse events (AEs) and Serious Adverse Events (SAEs) will be documented.

Expected Outcomes:

Positive results should provide justification to prolong the study to complete a phase III trial. This study is important because fatigue remains a cause of suffering amongst palliative patients with cancer. Modafinil has the potential to improve patients' fatigue, cognition, and quality of life.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Care Provider)

Primary Purpose:

Treatment

Official Title:

Modafinil to Improve Fatiguability (MODIFY): Modafinil vs. Placebo Vanguard RCT

Anticipated Study Start Date :

May 1, 2022

Anticipated Primary Completion Date :

May 1, 2023

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Modafinil One 200mg modafinil capsule once daily for one week	Drug: Modafinil Modafinil Other Names: Provigil
Placebo Comparator: Placebo One placebo capsule once daily for one week	Other: Placebo Placebo

Arm

Intervention/Treatment

Experimental: Modafinil

One 200mg modafinil capsule once daily for one week

Drug: Modafinil

Modafinil

Other Names:

Provigil

Placebo Comparator: Placebo

One placebo capsule once daily for one week

Other: Placebo

Placebo

Outcome Measures

Primary Outcome Measures

Fatigue [1 week]
Change in fatigue score evaluated using Multidimensional Fatigue Inventory (MFI).
Fatigue [1 week]
Change in fatigue score evaluated using Patient's Global Impression of Change (PGIC) score.
Recruitment rate [1 year]
The number of patients approached, total participants screened for eligibility, and reason for ineligibility or refusal to participate will be documented. We will consider the study successful if we can enroll 40 participants over a 1-year study period, with a recruitment rate of 15%.
Completion of intervention [1 year]
We will consider the intervention to be feasible if at least 75% of enrolled participants complete the full intervention protocol.
Completion of follow-up [1 year]
We will consider the intervention to be feasible if at least 75% of enrolled participants complete all assessments at 1- week follow-up.

Secondary Outcome Measures

Cognition [1 week]
Change in cognition score evaluated using the Fast Cognitive Evaluation (FaCE).
Cognition [1 week]
Change in cognition score evaluated using electronic cognitive assessment tool COVID-19 Assessment Battery.
Quality of life [1 week]
Change in quality of life score evaluated using McGill Quality of Life Questionnaire-Revised (MQOL-R).
Adverse events [1 week]
Daily patient-reported adverse effects with specific focus on headache, nausea and vomiting and anxiety, evaluated using the Common Terminology Criteria for Adverse Events (CTCAE).
Patient satisfaction with MFI [1 week]
Patient satisfaction with MFI as a measure of their fatigue on a 5-point Likert scale.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Stage III or IV cancer diagnosis;
Has been off cytotoxic chemotherapy for at least 1 month;
Eastern Cooperative Oncology Group (ECOG) score of 0-2;
Experiencing CRF, defined as score of 4 or greater on the Fatigue item of the Edmonton Symptom Assessment System-revised (ESAS-r);
Prognosis of at least 3 months;
Able to understand and communicate in English and/or French;
Able to give first-person informed consent.

Exclusion Criteria:

Allergy to modafinil;
Has been on stable dose of prednisone and/or dexamethasone for at least 3 days without dosing adjustments;
Received blood transfusion in the past week;
Hemoglobin lower than 100g/L for females or 110 g/L for males (measured in past month or at investigator's discretion);
Thyroid Stimulating Hormone (TSH) above normal range (measured in past month or at investigator's discretion);
Untreated or symptomatic brain metastasis or primary brain tumours;
Documented dementia diagnosis;
Documented major psychiatric illness including major depressive episode, bipolar disorder, or schizophrenia;
Uncontrolled hypertension, defined as blood pressure higher than 140/80;
Inability to ingest oral capsule;
Pregnant or lactating.