Aneurysmal Subarachnoid HemorrhagePhase 2NCT03209830
Pharmaceutical Treatment of Fatigue After Aneurysmal Subarachnoid Hemorrhage
A Phase 2 study testing OSU 6162 in people with Aneurysmal Subarachnoid Hemorrhage, run by Oslo University Hospital at 1 site in Norway.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Aneurysmal Subarachnoid Hemorrhage
- What is being tested?
- OSU 6162
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteNorway
- Study dates
- 5 Sep 2017to 13 Sep 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 20Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: OSU6162 in the Treatment of Fatigue and Other Neuropsychological Sequelae After Aneurysmal Subarachnoid Hemorrhage - A Double-blind, Randomised, Placebo-controlled Study
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.
Read the 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.
- Conditions
- Aneurysmal Subarachnoid Hemorrhage
- Being tested
- OSU 6162, Placebo Oral Tablet
- Keywords
- mental fatigue, drug therapy, subarachnoid hemorrhage, stroke
- Medical subject headings
- Subarachnoid Hemorrhage, Mental Fatigue, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OSU 6162Drug
Also called PNU-9639
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.
Placebo Oral TabletDrug
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 group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | OSU6162, drug given to half of the patients after randomization Receives: Drug: OSU 6162 |
| Arm B | Placebo comparator | Placebo oral tablet, drug given to halv of the patients after randomization Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Fatigue Severity Scale over time
FSS - change
Measured: Baseline, week 1, 4 12, and 20.
Secondary outcomes (15)
Beck Depression Inventory
BDI
Measured: Baseline, week 4, 12, and 20.
Beck Anxiety Inventory
BAI
Measured: Baseline, week 4, 12, and 20.
Mental Fatigue Scale
MFS
Measured: Baseline, week 4, 12, and 20.
Situational fatigue scale
SFS
Measured: Baseline, week 4, 12, and 20.
Short Form 36
SF-36
Measured: Baseline, week 4, 12, and 20.
Resilience Scale for Adults
RSA
Measured: Baseline, week 4, 12, and 20.
Brief COPE
B-COPE
Measured: Baseline, week 4, 12, and 20.
Symptom Checklist 90 Revised
SCL-90-R
Measured: Baseline, week 4, 12, and 20.
Post-traumatic stress symptom scale
PTSS-10
Measured: Baseline, week 4, 12, and 20.
Connors Performance Test Version 3
CPT-III
Measured: Baseline and week 12
Trail making Test (D-KEFS)
TMT
Measured: Baseline and week 12
Color-Word Interference Test (D-KEFS)
CWIT
Measured: Baseline and week 12
California Verbal Learning Test Version 2
CVLT-II
Measured: Baseline and week 12
Digit Span (WAIS-IV)
DS
Measured: Baseline and week 12
Grooved Pegboard (Halstead-Reitan Battery)
PEG
Measured: Baseline and week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2017
- Study start5 Sep 2017
- Primary completion13 Sep 2019
- Study completion13 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Aneurysmal Subarachnoid HemorrhageStudies of the same condition, open and under way.
- More trials run by Oslo University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double-blind, randomised, placebo-controlled study
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Göteborg University, Sahlgrenska University Hospital
- Responsible party
- Principal investigator, Angelika Sorteberg, Oslo University Hospital
- Investigators
- Angelika Sorteberg, MD, Principal investigator, Oslo University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03209830
- Sponsor's protocol ID
- 2016/2214
- Status last verified
- Nov 2019
- First submitted
- 28 Jun 2017
- Last updated
- 22 Nov 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- OSU6162 in the Treatment of Fatigue and Other Neuropsychological Sequelae After Aneurysmal Subarachnoid Hemorrhage - A Double-blind, Randomised, Placebo-controlled Study
- ClinicalTrials.gov ID
- NCT03209830
- Acronym / sponsor ID
- 2016/2214
- Conditions
- Aneurysmal Subarachnoid Hemorrhage
- Keywords
- mental fatigue, drug therapy, subarachnoid hemorrhage, stroke
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Oslo University HospitalUniversity, hospital or other
- Collaborators
- Göteborg University, Sahlgrenska University Hospital
- Study start
- 5 Sep 2017 (actual)
- Primary completion
- 13 Sep 2019 (actual)
- Study completion
- 13 Sep 2019 (actual)
- First posted
- 6 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Double-blind, randomised, placebo-controlled study
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: OSU 6162OSU6162, drug given to half of the patients after randomization |
| Arm B | Placebo comparator | Drug: Placebo Oral TabletPlacebo oral tablet, drug given to halv of the patients after randomization |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (20 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OSU 6162Also: PNU-9639All 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. | Drug | Arm A |
| Placebo Oral TabletAll 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. | Drug | Arm B |
Primary outcome
Change in Fatigue Severity Scale over time
Time frame: Baseline, week 1, 4 12, and 20.
FSS - change
15 secondary outcomes
Beck Depression Inventory
Time frame: Baseline, week 4, 12, and 20.
Beck Anxiety Inventory
Time frame: Baseline, week 4, 12, and 20.
Mental Fatigue Scale
Time frame: Baseline, week 4, 12, and 20.
Situational fatigue scale
Time frame: Baseline, week 4, 12, and 20.
Short Form 36
Time frame: Baseline, week 4, 12, and 20.
Resilience Scale for Adults
Time frame: Baseline, week 4, 12, and 20.
Brief COPE
Time frame: Baseline, week 4, 12, and 20.
Symptom Checklist 90 Revised
Time frame: Baseline, week 4, 12, and 20.
Post-traumatic stress symptom scale
Time frame: Baseline, week 4, 12, and 20.
Connors Performance Test Version 3
Time frame: Baseline and week 12
Trail making Test (D-KEFS)
Time frame: Baseline and week 12
Color-Word Interference Test (D-KEFS)
Time frame: Baseline and week 12
California Verbal Learning Test Version 2
Time frame: Baseline and week 12
Digit Span (WAIS-IV)
Time frame: Baseline and week 12
Grooved Pegboard (Halstead-Reitan Battery)
Time frame: Baseline and week 12
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Angelika Sorteberg, MD principal investigator
Oslo University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing OSU 6162 in people with Aneurysmal Subarachnoid Hemorrhage, run by Oslo University Hospital at 1 site in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Fatigue Severity Scale over time (time frame: Baseline, week 1, 4 12, and 20.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2019.