Modafinil to Improve Fatiguability

Last updated: January 9, 2026
Sponsor: Ottawa Hospital Research Institute
Overall Status: Active - Recruiting

Phase

1/2

Condition

Mild Cognitive Impairment

Pain (Pediatric)

Neoplasms

Treatment

Placebo

Modafinil

Clinical Study ID

NCT05333250
663439
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. 18 years of age or older with stage III or IV cancer diagnosis

  2. Estimated prognosis ≥ 3 months

  3. Eastern Cooperative Oncology Group (ECOG) Score 0-2

  4. Experiencing cancer-related fatigue, defined as a score of 4 or greater on theFatigue item of the Edmonton Symptom Assessment System-revised-constipation/sleep (ESAS-r-cs)

  5. Ability to understand and communicate in English

  6. Ability to give first-person informed consent

Exclusion

Exclusion Criteria:

  • Currently receiving or have received cytotoxic chemotherapy in the last 6 weeks

  • Allergy to modafinil or placebo contents

  • Dose change of prednisone or dexamethasone in the past 7 days or planned dose changeduring study period

  • Blood transfusion in the last 2 weeks

  • Hemoglobin lower than 80 g/L measured in the last 4 weeks

  • TSH above normal range in the last 4 weeks

  • Severe liver dysfunction (total bilirubin >3x upper limit of normal, or aspartateaminotransferase or alanine aminotransferase >5x upper limit of normal)

  • Known brain metastasis or primary brain tumor

  • Documented dementia diagnosis

  • Documented major psychiatric illness including major depressive episode, bipolardisorder, schizophrenia

  • Uncontrolled hypertension as defined by a blood pressure greater than 140/90mmHg

  • Unstable angina

  • Recent (<6 months previous) myocardial infarction

  • Evidence of left ventricular hypertrophy or ischemia on ECG

  • Arrythmia (e.g., atrial fibrillation)

  • Coronary artery disease with Canadian Cardiovascular Society Symptoms Class >1

  • Taking high dose selective serotonin reuptake inhibitors (SSRIs) or tricyclicantidepressants

  • Taking any benzodiazepine at any dose

  • Taking any amphetamine at any dose

  • Taking any monoamine oxidase inhibitor (MAOI) at any dose

  • Taking any azole anti-fungal medication (e.g., fluconazole, itraconazole, orketoconazole)

  • Taking any of the following medications at any dose:

  1. Methylphenidate

  2. Cyclosporine

  3. Propranolol

  4. Phenytoin

  5. S-mephenytoin

  6. Warfarin

  7. Triazolam

  8. Ethinyl estradiol

  9. Clomipramine

  10. Midodrine

  11. Antipyrine

  • Inability to ingest oral capsule

  • Pregnancy or lactation, or trying to conceive

  • Any other history, condition, therapy, or uncontrolled intercurrent illness whichcould, in the opinion of the Qualified Medical Investigator, affect compliance withstudy requirements or which would make the participant unsuitable for this study.

  • Simultaneous participation in another interventional clinical study (e.g., Phase 1-3clinical studies) or treatment with any investigational medicinal product within 30days prior to screening visit that could, in the judgment of the Qualified MedicalInvestigator, affect the patient's participation in or outcome of this clinicaltrial.

Study Design

Total Participants: 40
Treatment Group(s): 2
Primary Treatment: Placebo
Phase: 1/2
Study Start date:
January 22, 2026
Estimated Completion Date:
March 31, 2028

Study 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:

  1. To estimate the effect size of modafinil in managing CRF and CRCI

  2. 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.

Connect with a study center

  • The Ottawa Hospital

    Ottawa, Ontario
    Canada

    Site Not Available

  • The Ottawa Hospital

    Ottawa 6094817, Ontario 6093943
    Canada

    Active - Recruiting

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