None listed
Conditions
Brief summary
This is a Multicentre, prospective, randomised, placebo-controlled, double-blind, parallel group phase III trial with an adaptive sample size re-estimation in stroke survivors enrolled 3 or more months after their event. The primary objective is to test the hypothesis that in stroke survivors, 200mg of modafinil taken once daily for at least 56 days significantly improves participant quality of life compared to placebo, due to the improvement of severe and persisting fatigue after stroke. The trial will screen potential participants with the Multidimensional Fatigue Inventory (MFI) score of above 60. Upon consent and if patient meets other specified inclusion and exclusion criteria they will be randomised to either modafinil (200mg) or placebo once daily for 56 days. The main study visits include screening, Day 0, Day 28 and Day 56 for trial assessments with the SF-36, TMTs, FSS, MoCA, DASS 42 and the EQ5D and mRS. Caregivers will also be compete CSI and OCBS at each study visit The study sample size has been calculated to be 300 recruited participants (150 in each arm). There are three optional sub-studies. 1. Open-Label modafinil for an additional 10 months and return to the study centre for trial assessments after the 10-month treatment phase. 2. Physical activity monitoring and 3. Cognitive assessments
Interventions
Study Drug: Modafinil
Dose: 200mg taken once a day for 56 days followed by open-label non-randomised
observational phase for 10 months.
Route: oral tablet
Time of administration; Modafinil is ideally to be taken with breakfast.
Treatment adherence will be monitored by drug tablet return.
Sponsors
The Florey Institute of Neuroscience and Mental Health (The Florey)
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participant: • 18 years of age or older • have suffered a stroke (ischaemic/ Haemorrhagic) at least 3 months ago • have persistent self-reported fatigue with MFI score of 60 or more • modified Rankin Score (mRS) of 3 or less • can speak reasonable English, understand instructions and be able to complete tests and questionnaires on their own or with minimal support • able to give informed consent to participate in the study, in accordance with the ICH GCP guidelines, and local regulations, before initiating any study related procedures Caregiver: • have the consent of the study participant for whom they care for, to take part in the research • meets the definition of a ‘caregiver’ to participate in the research. They must be a reliable and capable person, who either lives in the same household with the participant or interacts with the participant at least 10 hours per week and will be available to attend all clinic visits with them in person. • able to give informed consent to participate in the study, in accordance with the ICH GCP guidelines, and local regulations, before initiating any study related procedures
Exclusion criteria
•an active, symptomatic or untreated anxiety disorder who, based on the clinical judgement of the investigator, could be prone to an exacerbation of anxiety with the use of modafinil (Note: Subjects with well-controlled anxiety who are on medication are eligible for consideration for inclusion in the trial) • an active, symptomatic or untreated depression who, based on the clinical judgement of the investigator could be prone to an exacerbation of depression or the development of agitation (Note: Subjects with well-controlled depression who are stable and/or have been on antidepressant medication for at least 6 months are eligible for consideration for inclusion in the trial) • pre-existing dementia or other neuropsychiatric disease • other diagnoses with fatigue as a known symptom e.g. chronic fatigue syndrome, multiple sclerosis, narcolepsy • current or past drug abuse • known contraindication to treatment with modafinil • known active malignancy, intracranial tumour, subdural or epidural hematoma • severe renal or hepatic impairment (GFR <15mL/min) • Unstable or poorly controlled epilepsy where the investigator is concerned about the potential for drug interactions. • benzodiazepines or other hypnosedative drugs which may interact with modafinil as per specific medication guidance • clinical suspicion of sleep apnoea. If the investigator suspects on clinical grounds, that fatigue is related to sleep apnoea, an Epworth Sleepiness Scale must be undertaken. If the score is >10, overnight pulse oximetry monitoring or a sleep study must be undertaken to exclude sleep apnoea. • participant is receiving immunosuppressive therapy or has a known immunodeficiency state, e.g., HIV. • pregnant or breastfeeding women. Women of child bearing potential will need to have a negative pregnancy test at screening and should agree to using an acceptable barrier form of birth control. The effectiveness of steroidal contraceptives (contraceptive pill, implants, intrauterine devices (IUDs) or patches, etc.) may be impaired due to induction of CYP3A4/5 by modafinil. Alternative or concomitant methods of contraception are recommended for patients treated with modafinil. Acceptable methods of contraception should continue to be used for at least two months after ingestion of the final study dose.
Outcome results
None listed