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Pharmaceutical Treatment of Fatigue After Aneurysmal Subarachnoid Hemorrhage

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ClinicalTrials.gov Identifier: NCT03209830
Recruitment Status : Recruiting
First Posted : July 6, 2017
Last Update Posted : September 5, 2018
Sponsor:
Collaborators:
Göteborg University
Sahlgrenska University Hospital, Sweden
Information provided by (Responsible Party):
Angelika Sorteberg, Oslo University Hospital

Tracking Information
First Submitted Date  ICMJE June 28, 2017
First Posted Date  ICMJE July 6, 2017
Last Update Posted Date September 5, 2018
Actual Study Start Date  ICMJE September 5, 2017
Estimated Primary Completion Date November 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 3, 2017)
Change in Fatigue Severity Scale over time [ Time Frame: Baseline, week 1, 4 12, and 20. ]
FSS - change
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03209830 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 3, 2017)
  • Beck Depression Inventory [ Time Frame: Baseline, week 4, 12, and 20. ]
    BDI
  • Beck Anxiety Inventory [ Time Frame: Baseline, week 4, 12, and 20. ]
    BAI
  • Mental Fatigue Scale [ Time Frame: Baseline, week 4, 12, and 20. ]
    MFS
  • Situational fatigue scale [ Time Frame: Baseline, week 4, 12, and 20. ]
    SFS
  • Short Form 36 [ Time Frame: Baseline, week 4, 12, and 20. ]
    SF-36
  • Resilience Scale for Adults [ Time Frame: Baseline, week 4, 12, and 20. ]
    RSA
  • Brief COPE [ Time Frame: Baseline, week 4, 12, and 20. ]
    B-COPE
  • Symptom Checklist 90 Revised [ Time Frame: Baseline, week 4, 12, and 20. ]
    SCL-90-R
  • Post-traumatic stress symptom scale [ Time Frame: Baseline, week 4, 12, and 20. ]
    PTSS-10
  • Connors Performance Test Version 3 [ Time Frame: Baseline and week 12 ]
    CPT-III
  • Trail making Test (D-KEFS) [ Time Frame: Baseline and week 12 ]
    TMT
  • Color-Word Interference Test (D-KEFS) [ Time Frame: Baseline and week 12 ]
    CWIT
  • California Verbal Learning Test Version 2 [ Time Frame: Baseline and week 12 ]
    CVLT-II
  • Digit Span (WAIS-IV) [ Time Frame: Baseline and week 12 ]
    DS
  • Grooved Pegboard (Halstead-Reitan Battery) [ Time Frame: Baseline and week 12 ]
    PEG
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmaceutical Treatment of Fatigue After Aneurysmal Subarachnoid Hemorrhage
Official Title  ICMJE OSU6162 in the Treatment of Fatigue and Other Neuropsychological Sequelae After Aneurysmal Subarachnoid Hemorrhage - A Double-blind, Randomised, Placebo-controlled Study
Brief Summary Many people who have undergone subarachnoid hemorrhage from an aneurysm (an artery of a vein in the brain) struggle with a pronounced fatigue as well as a number of other sequelae such as impaired concentration, memory deficits and emotional problems. Exhaustion is often permanent and can lead to a significant worsening of quality of life and be the cause of disability. This condition does not only have major consequences for the individual who is affected, but also for their families and for society. So far no effective treatment for fatigue has been found. The drug OSU6162 has shown a beneficial effect on fatigue and other impairments after stroke and after traumatic brain injury. There is good reason to believe that OSU6162 can also improve fatigue and other impairments after aneurysm bleeding and thus increase the chance of returning to the level of daily function they had before the bleeding. The study is double blinded and measures the effect of OSU6162 and placebo on fatigue and neuropsychological function.
Detailed Description

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. The eventual aim is to find a cure for the debilitating fatigue, cognitive and emotional problems arising in many of the individuals that have suffered aSAH. Until now, no effective treatment exists and the final goal is to provide a medical treatment that alleviates these symptoms to such an extend that aSAH patients can regain a normal quality of live and resume their pre-morbid occupational status and level of social participation.

The study is a phase II, double-blind, randomised, placebo-controlled study.

Patients that have undergone aSAH from Health-region South-East. All aSAH patients in Health-region South-East are treated at Oslo University Hospital, Neuroclinic, at the Departments of Neurosurgery and the Department of Physical Medicine and Rehabilitation and will be recruited from there. 100 patients will be included in this trial (50 in each group).

All patients will receive a dose of OSU6162 15 mg or placebo BID. The expected duration of therapy is 12 weeks.

The primary endpoint will be change from baseline in Fatigue Severity Scale (FSS) after 12 weeks of treatment with OSU6162 or placebo, with data collection at weeks 1, 4, 12, and 20 (20=8 weeks after treatment).

The secondary endpoints include change from baseline in total score on a number of questionnaires, with data collection at week 4, 12, and 20 (i.e. at 8 weeks after treatment).

Secondary endpoints include change from baseline in vital signs, adverse events (+ week 4), physical examinations, blood and urine samples at week 1 and 12.

Secondary endpoints include change from baseline on a number of neuropsychological tests, with data collection at week 12.

Statistical analyses will be based on linear mixed models. A mixed model analysis uses all the available data to compensate for the data missing on a particular patient. Thus any imputation techniques for missing data points are not necessary.

Adverse events (AEs) will be coded using Medical Dictionary for Regulatory Activities (MedDRA) and tabulated by System Organ Class (SOC) and preferred term.

A data monitoring committee (DMC) will be established in order to enhance the safety aspect of the study and its primary function will be to review all registered side-effects at various points of time along the study and consider if there are indications for early stopping (either for futility or for positive efficacy).

The study will be conducted in accordance with ethical principles that have their origin in the Declaration of Helsinki and are consistent with ICH/Good Clinical Practice and applicable regulatory requirements. Registration of patient data will be carried out in accordance with national personal data laws.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Double-blind, randomised, placebo-controlled study
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Aneurysmal Subarachnoid Hemorrhage
Intervention  ICMJE
  • Drug: OSU 6162
    All patients will receive a dose of OSU6162 15 mg BID x 2 per day. The expected duration of therapy is 12 weeks. After 1 week of treatment, patients who do not respond to treatment will have their dose increased to maximum 30 mg BID x 2 per day.
    Other Name: PNU-9639
  • Drug: Placebo Oral Tablet
    All patients will receive a dose of placebo 15 mg BID x 2 per day. The expected duration of therapy is 12 weeks. After 1 week of treatment, patients who do not respond to treatment will have their dose increased to maximum 30 mg BID x 2 per day.
Study Arms  ICMJE
  • Experimental: Arm A
    OSU6162, drug given to half of the patients after randomization
    Intervention: Drug: OSU 6162
  • Placebo Comparator: Arm B
    Placebo oral tablet, drug given to halv of the patients after randomization
    Intervention: Drug: Placebo Oral Tablet
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 3, 2017)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2019
Estimated Primary Completion Date November 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Patients that have undergone aneurysmal subarachnoid hemorrhage (aSAH) from Health-region South-East.

Inclusion Criteria:

  • Signed written informed consent
  • > 18 years old
  • Aneurysmal subarachnoid haemorrhage >12 months prior to the start of the study.
  • Diagnosed with post SAH syndrome/fatigue at ≥12 months after their hemorrhage
  • 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)

Exclusion Criteria:

  • Residual symptoms following other pathologies than aSAH
  • Not adequately treated hydrocephalus secondary to aSAH
  • Diagnosed with epilepsy, neurodegenerative disease, cerebral paresis, tumor cerebri, cerebral arterio-venous malformations
  • Patients that have undergone brain surgery, have been hospitalized for head trauma, or suffered intracranial hemorrhage, stroke, or infectious brain diseases within the last 12 months
  • Active substance abuse (drug screen taken at baseline)
  • Current pregnancy or breast-feeding, or intention to become pregnant within 3 months after the last dose
  • Women of childbearing age not using contraceptives
  • Pathologic ECG, as assessed by the investigator. Max QTc-time on ECG in excess of 480 ms or any of these conditions that can increase QT related incidences: long QT syndrome or family history of long QT syndrome, hypothyreoidism, hypocalcemia, significant potassium deviations, type 1 diabetes with prolonged QT, and cardiac insufficiency
  • Abnormal laboratory values of such severity that participation in the study, in the opinion of the investigator, is questionable
  • 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
  • Patients that speak so poorly Norwegian that they are not able to answer the questionnaires or undergo neuropsychological testing
  • Previous treatment with OSU6162
  • 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
  • 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.
  • Any surgical or medical condition which, in the opinion of the investigator, might interfere with the absorption, distribution, metabolism or excretion of OSU6162
  • 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
  • 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)
  • Antipsychotic treatment
  • 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.
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Angelika Sorteberg, MD 92629544 asortebe@ous-hf.no
Contact: Elin Western, PhD 95915180 elinwe@ous-hf.no
Listed Location Countries  ICMJE Norway
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03209830
Other Study ID Numbers  ICMJE 2016/2214
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Angelika Sorteberg, Oslo University Hospital
Study Sponsor  ICMJE Oslo University Hospital
Collaborators  ICMJE
  • Göteborg University
  • Sahlgrenska University Hospital, Sweden
Investigators  ICMJE
Principal Investigator: Angelika Sorteberg, MD Oslo University Hospital
PRS Account Oslo University Hospital
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP