Fatigue and neuropsychological dysfunction after aneurysmal brain hemorrhage
Conditions
Interventions
Product Code: OSU6162
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
Sponsors
Oslo University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent 2. > 18 years old 3. Aneurysmal subarachnoid haemorrhage >12 months prior to the start of the study. 4. Diagnosed with post SAH syndrome/fatigue at =12 months after their hemorrhage 5. Post-menopausal or using adequate contraceptive measures - Female patients of childbearing potential using a highly efficient method of contraception (i.e. a method with a failure rate of less than 1% [e.g. sterilisation, hormone implants, hormone injections, some intrauterine devices, or vasectomy in partner]) - Male patients agreeing to use condoms during the study and for 3 months after the end of the study/last dose of the investigational medicinal product, or male patients with a partner who is using a highly efficient method of contraception (as described above) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 70 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1. Residual symptoms following other pathologies than aSAH 2. Not adequately treated hydrocephalus secondary to aSAH 3. Diagnosed with neurodegenerative disease 4. Active substance abuse (drug screen taken at baseline) 5. Current pregnancy or breast-feeding, or intention to become pregnant within 3 months after the last dose 6. Women of childbearing age not using contraceptives 7. Pathologic ECG, as assessed by the investigator. Max QTc-time on ECG: 450 ms in men and 460 ms in women 8. Abnormal laboratory values of such severity that participation in the study, in the opinion of the investigator, is questionable 9. Patients who are so debilitated by their disease that they are not assumed to be able to perform the assessments or handle the instruments used for evaluation of effect and/or are not able to consent 10. Patients that speak so poorly Norwegian that they are not able to answer the questionnaires or undergo neuropsychological testing 11. Previous treatment with OSU6162 12. Clinically significant liver disease which may prevent the patient from completing the study and/or an elevation in either total bilirubin, alkaline phosphatase, LDH, SGOT of >2 times the laboratory reference 13. Clinically significant renal disease which may prevent the patient from completing the study and/or an elevation in serum creatinine of >1.5 times the laboratory reference. 14. Any surgical or medical condition which, in the opinion of the investigator, might interfere with the absorption, distribution, metabolism or excretion of OSU6162 15. Patients treated with Modiodal, Xyrem, Mirtazapine, Mianserin or metabolic enzyme inhibitors or inducers, or drugs with a narrow treatment window (e.g. warfarin, antiepileptics, cyclosporine) and individually modelled drugs such as lithium 16. Use of drugs capable of inducing hepatic enzyme metabolism (e.g., barbiturates, rifampicin, carbamazepine, phenytoin, primidone) within 30 days prior to the start of the study (or 5 half-lives of the inducing agent, whichever is longer) 17. Antipsychotic treatment 18. Patients treated with “unstable therapies”, i.e., treatments that have not been at the same dose for at least 6 weeks prior to inclusion in this study. The treatment must also remain unchanged during the study period. Insomnia medication and other PRN medications are allowed. 19. Use of acute or chronic medications for other medical conditions are allowed based on the investigator’s judgement. Occasional use of over-the-counter (OTC) medication is not allowed during the study or one month prior to inclusion.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate the efficacy of OSU6162 with respect to sequela after aneurysmal subarachnoid haemorrhage with special emphasis on fatigue.;Secondary Objective: Key secondary objective is the safety and tolerability of OSU6162;Primary end point(s): The primary endpoint will be change from baseline in improvement score on Global Clinical Impression of Change (CGI-C) ;Timepoint(s) of evaluation of this end point: After 12 weeks of treatment with OSU6162 or placebo, with data collection at weeks 1, 6, 12, and 20 (20=8 weeks after treatment). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints include change from baseline in total score on the following questionnaires: - Beck Depression Inventory (BDI) - Beck Anxiety Inventory (BAI) - Mental Fatigue Scale (MFS) - Fatigue Severity Scale (FSS) - Situational fatigue scale (SFS) - Short Form 36 (SF-36) - Resilience Scale for Adults (RSA) - Brief COPE - Symptom Checklist 90 (SCL-90) - Post-traumatic symptom scale (PTSS-10) at week 6, 12, and 20 (i.e. at 8 weeks after treatment) - Plasma concentration of OSU6162 at 12 weeks Secondary endpoints include change from baseline in vital signs, adverse events (+ week 6), physical examinations, blood and urine samples at week 1, 8 and 12 Secondary endpoints include change from baseline in these neuropsychological tests: - Connors performance test (CPT) - Delis-Kaplan Executive Function System (D-KEFS): Trail Making Test Color-Word Interference Test - California Verbal Learning Test (CVLT-II) - Digit span from Wechsler Adult Intelligence Scale (WAIS-IV) - Grooved Pegboard at week 12 ;Timepoint(s) of evaluation of this end point: Questionnaires after 6 and 12 weeks of treatment and 8 weeks after treatment. Neuropsychological tests after 12 weeks of treatment | — |
Countries
Norway
Contacts
Public ContactRikshospitalet, Dept.of Neurosurger
Oslo University Hospital
Outcome results
None listed