Stress Disorders, Post-traumaticPhase 2AFTERNCT01814332
Analyzing Female Trauma Exposed Responses to a Medication
A Phase 2 study testing GSK561679 in people with Stress Disorders, Post-traumatic, run by VA Office of Research and Development at 1 site in United States.
Trial summary
This purpose of this study is to look at the safety of the experimental drug GSK561679 as well as its effects on PTSD symptoms, thinking and memory, startle reaction, stress hormones, and mental health symptoms in comparison to placebo (an inactive substance). Read more about this study
- Who is it for?
- Ages 18 to 65 years, women only
- Conditions the study is for
- Stress Disorders, Post-traumatic
- What is being tested?
- GSK561679
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 128 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2010to 31 Oct 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female between 18-65 years of age
- Able to provide consent and willing to participate in research
- PTSD duration of illness at least 3 months
- Negative Urine toxicology test
- Agrees to use protocol-defined effective birth control method
Who cannot join
- Subject is currently participating in another clinical trial in which she is or will be exposed to an investigational or non-investigational drug or device, or has done so within the preceding month for studies unrelated to PTSD, or 1 month for studies related to PTSD
- Subject has a documented history of hepato-biliary disease including a history of, or positive laboratory results for hepatitis
- Subject requires ongoing treatment with medications that are prohibited per protocol
- Subject has a stool positive for occult blood.
- Pregnancy or lactation
Trial locations and contacts
1 site in 1 country.
United States1 site
San Francisco VA Medical Center, San Francisco, CA
San Francisco, California, 94121
About this study
Official title: CRF Receptor Antagonist for PTSD and Related Sleep Disturbances in Women
This purpose of this study is to look at the safety of the experimental drug GSK561679 as well as its effects on PTSD symptoms, thinking and memory, startle reaction, stress hormones, and mental health symptoms in comparison to placebo (an inactive substance).
Read the detailed description
A growing body of literature suggests that stress-related disorders such as PTSD are associated with chronically increased activity of CNS circuits that utilize corticotropin-releasing factor (CRF), a neuropeptide involved in mediating the neuroendocrine, immune, autonomic, and behavioral responses to stress. CRF1 receptor antagonists exert significant dampening effects on this system, but have never been investigated in patients with PTSD. The investigators at Mount Sinai School of Medicine (MSSM) and the National Institute of Mental Health (NIMH) Intramural Research Program have conducted a Phase II proof-of-concept clinical trial of a neurokinin-1 antagonist provided by GlaxoSmithKline (GSK). In this investigation, we will conduct a 2-site (Emory and MSSM), 6-week, randomized, double-blind, placebo-controlled, parallel-arm, fixed dose trial evaluating the efficacy, safety, and tolerability of GSK561679 for 154 female adult outpatients with PTSD. The San Francisco Department of Veterans Affairs Medical Center (SFVAMC) was added as a site in July 2012. SFVAMC will enroll 40 female adult outpatients with PTSD.
We propose to investigate the efficacy of the highly specific CRF1 antagonist GSK561679 in PTSD in a placebo-controlled clinical trial. GSK561679 has not been approved by the Food and Drug Administration for the treatment of any condition. Furthermore, we propose to longitudinally investigate whether certain biological surrogate markers (neuroendocrine, neurophysiology, genotyping) are predictive of treatment response. If a patient is already taking medication for PTSD and has achieved therapeutic response, she will not be tapered off effective medication(s) to participate in this study, and will not be eligible for the study. Taper and discontinuation of medications in preparation for this study will only occur in those patients who are not responding to medication treatment for PTSD.
Preclinical and clinical literature also exists which implicates both hypothalamic and extra hypothalamic CRF in stress-related insomnia and the regulation of non-rapid eye movement delta sleep. There is preliminary evidence that blocking CRF signaling results in an immediate improvement in stress-related sleep disturbances. Disturbed sleep is the most prevalent symptom endorsed by PTSD patients. It is potentially debilitating in many domains of functioning, and it is an outcome that can be objectively and precisely measured with sleep EEG. Therefore, an exploratory aim of this study will be to investigate the impact of GSK561679 on objective measures of sleep continuity and quantitative sleep EEG using ambulatory polysomnography. All subjects enrolled at SFVAMC who meet inclusion and exclusion criteria for the study will be given the option of having their sleep monitored throughout the study
- Conditions
- Stress Disorders, Post-traumatic
- Being tested
- GSK561679, Placebo
- Keywords
- Stress disorders, Post-traumatic, Sleep
- Medical subject headings
- Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK561679Drug
Also called CRF1 antagonist
GSK561679, oral administration, 350mg/day, 6 week administration
PlaceboDrug
Also called Sugar pill
Placebo compound treatment for comparison with IP
| Study group | Role | What they receive |
|---|---|---|
| GSK561679 | Experimental | GSK561679, oral administration, 350mg/day, 6 week administration Receives: Drug: GSK561679 |
| Placebo | Placebo comparator | Placebo compound treatment for comparison with IP Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy, Measured by Change in the Clinician-Administered PTSD Scale (CAPS) Score
The CAPS is a semi-structured clinical interview providing a measure of the severity of PTSD symptoms. A severity score is calculated by summing the frequency and intensity scores for each of the 17 DSM-IV criteria symptoms. The severity of symptoms is rated on a scale from 0-4, where, 0 = Absent, 1 = Mild/subthreshold; 2 = Moderate/ threshold, 3 = Severe/markedly elevated and 4 = Extreme/ incapacitating. Scores may range from 0 (no symptoms) to 136 (severe symptoms). Change is the difference in scores between baseline and 6 weeks.
Measured: Baseline, 6 weeks
Secondary outcomes (3)
Efficacy, Measured by Response Rate of at Least 50% Improvement in CAPS Score at the End of 6 Weeks as Compared to Baseline
The number of participants that showed at least a 50% reduction in CAPS scores from their baseline visit at the end of 6 weeks were measured as having a response to the treatment. The CAPS is a semi-structured clinical interview providing a measure of the severity of PTSD symptoms. A severity score is calculated by summing the frequency and intensity scores for each of the 17 DSM-IV criteria symptoms. Scores may range from 0 (no symptoms) to 136 (severe symptoms).
Measured: Baseline, Week 6
Efficacy, Measured by Change in the Montgomery-Asberg Depression Rating Scale (MADRS) Score
The MADRS is a ten-item clinician-administered questionnaire used to measure the severity of depressive symptoms in patients with depressive disorders. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. Change is the difference in scores between baseline and 6 weeks.
Measured: Baseline, Week 6
Safety, Measured by the Number of Subjects That Experienced an Adverse Event
The occurrence of adverse events will be recorded at the end of 6 weeks.
Measured: Baseline, Week 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2013 (estimated)
- Study start1 Jan 2010
- Primary completion30 Jun 2014
- Study completion31 Oct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Stress Disorders, Post-traumaticStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe 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
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 128 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Thomas C. Neylan, MD, Principal investigator, San Francisco VA Medical Center, San Francisco, CA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01814332
- Sponsor's protocol ID
- 09S-NIMH-002
- Acronym
- AFTER
- Status last verified
- Jun 2021
- First submitted
- 11 Mar 2013
- Last updated
- 25 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CRF Receptor Antagonist for PTSD and Related Sleep Disturbances in Women
- ClinicalTrials.gov ID
- NCT01814332
- Acronym / sponsor ID
- AFTER / 09S-NIMH-002
- Conditions
- Stress Disorders, Post-traumatic
- Keywords
- Stress disorders, Post-traumatic, Sleep
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 128 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 1 Jan 2010 (actual)
- Primary completion
- 30 Jun 2014 (actual)
- Study completion
- 31 Oct 2014 (actual)
- First posted
- 19 Mar 2013 (estimated)
- Results
- Posted 25 Apr 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This purpose of this study is to look at the safety of the experimental drug GSK561679 as well as its effects on PTSD symptoms, thinking and memory, startle reaction, stress hormones, and mental health symptoms in comparison to placebo (an inactive substance).
Detailed description
A growing body of literature suggests that stress-related disorders such as PTSD are associated with chronically increased activity of CNS circuits that utilize corticotropin-releasing factor (CRF), a neuropeptide involved in mediating the neuroendocrine, immune, autonomic, and behavioral responses to stress. CRF1 receptor antagonists exert significant dampening effects on this system, but have never been investigated in patients with PTSD. The investigators at Mount Sinai School of Medicine (MSSM) and the National Institute of Mental Health (NIMH) Intramural Research Program have conducted a Phase II proof-of-concept clinical trial of a neurokinin-1 antagonist provided by GlaxoSmithKline (GSK). In this investigation, we will conduct a 2-site (Emory and MSSM), 6-week, randomized, double-blind, placebo-controlled, parallel-arm, fixed dose trial evaluating the efficacy, safety, and tolerability of GSK561679 for 154 female adult outpatients with PTSD. The San Francisco Department of Veterans Affairs Medical Center (SFVAMC) was added as a site in July 2012. SFVAMC will enroll 40 female adult outpatients with PTSD.
We propose to investigate the efficacy of the highly specific CRF1 antagonist GSK561679 in PTSD in a placebo-controlled clinical trial. GSK561679 has not been approved by the Food and Drug Administration for the treatment of any condition. Furthermore, we propose to longitudinally investigate whether certain biological surrogate markers (neuroendocrine, neurophysiology, genotyping) are predictive of treatment response. If a patient is already taking medication for PTSD and has achieved therapeutic response, she will not be tapered off effective medication(s) to participate in this study, and will not be eligible for the study. Taper and discontinuation of medications in preparation for this study will only occur in those patients who are not responding to medication treatment for PTSD.
Preclinical and clinical literature also exists which implicates both hypothalamic and extra hypothalamic CRF in stress-related insomnia and the regulation of non-rapid eye movement delta sleep. There is preliminary evidence that blocking CRF signaling results in an immediate improvement in stress-related sleep disturbances. Disturbed sleep is the most prevalent symptom endorsed by PTSD patients. It is potentially debilitating in many domains of functioning, and it is an outcome that can be objectively and precisely measured with sleep EEG. Therefore, an exploratory aim of this study will be to investigate the impact of GSK561679 on objective measures of sleep continuity and quantitative sleep EEG using ambulatory polysomnography. All subjects enrolled at SFVAMC who meet inclusion and exclusion criteria for the study will be given the option of having their sleep monitored throughout the study
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GSK561679 | Experimental | Drug: GSK561679GSK561679, oral administration, 350mg/day, 6 week administration |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo compound treatment for comparison with IP |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Female between 18-65 years of age
- Able to provide consent and willing to participate in research
- PTSD duration of illness at least 3 months
- Negative Urine toxicology test
- Agrees to use protocol-defined effective birth control method
Key exclusion criteria (5 listed)
- Subject is currently participating in another clinical trial in which she is or will be exposed to an investigational or non-investigational drug or device, or has done so within the preceding month for studies unrelated to PTSD, or 1 month for studies related to PTSD
- Subject has a documented history of hepato-biliary disease including a history of, or positive laboratory results for hepatitis
- Subject requires ongoing treatment with medications that are prohibited per protocol
- Subject has a stool positive for occult blood.
- Pregnancy or lactation
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 |
|---|---|---|
| GSK561679Also: CRF1 antagonistGSK561679, oral administration, 350mg/day, 6 week administration | Drug | GSK561679 |
| PlaceboAlso: Sugar pillPlacebo compound treatment for comparison with IP | Drug | Placebo |
Primary outcome
Efficacy, Measured by Change in the Clinician-Administered PTSD Scale (CAPS) Score
Time frame: Baseline, 6 weeks
The CAPS is a semi-structured clinical interview providing a measure of the severity of PTSD symptoms. A severity score is calculated by summing the frequency and intensity scores for each of the 17 DSM-IV criteria symptoms. The severity of symptoms is rated on a scale from 0-4, where, 0 = Absent, 1 = Mild/subthreshold; 2 = Moderate/ threshold, 3 = Severe/markedly elevated and 4 = Extreme/ incapacitating. Scores may range from 0 (no symptoms) to 136 (severe symptoms). Change is the difference in scores between baseline and 6 weeks.
3 secondary outcomes
Efficacy, Measured by Response Rate of at Least 50% Improvement in CAPS Score at the End of 6 Weeks as Compared to Baseline
Time frame: Baseline, Week 6
Efficacy, Measured by Change in the Montgomery-Asberg Depression Rating Scale (MADRS) Score
Time frame: Baseline, Week 6
Safety, Measured by the Number of Subjects That Experienced an Adverse Event
Time frame: Baseline, Week 6
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Thomas C. Neylan, MD principal investigator
San Francisco VA Medical Center, San Francisco, CA
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 GSK561679 in people with Stress Disorders, Post-traumatic, run by VA Office of Research and Development at 1 site in United States.
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 5 inclusion and 5 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 25 Jun 2021. 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 United States. 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?
Yes. Results are posted in the registry (first posted 25 Apr 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Efficacy, Measured by Change in the Clinician-Administered PTSD Scale (CAPS) Score (time frame: Baseline, 6 weeks). 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 25 Jun 2021.