Anxiety DisordersNCT01059227
Effects of a CRF1 Receptor Antagonist on Human Startle in Normal Female Volunteers
An observational study of Anxiety Disorders, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
Background: Research has shown that the hormone corticotropin-releasing hormone (CRH) is involved in stress and anxiety, and that drugs that block the effect of CRH in the body can reduce anxiety. GSK561679 is an experimental drug that attempts to reduce anxiety by blocking the effect of CRH. Read more about this study
- Who is it for?
- Ages 21 to 50 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Anxiety Disorders
- How many people
- 39 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Jan 2010to 14 Aug 2015
- Phase
- Observational
- 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 21 to 50 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- HEALTHY FEMALE VOLUNTEERS as determined by a responsible physician, based on a medical evaluation including own and familial medical history, physical examination, psychiatric history, psychiatric evaluation, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator agrees that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Females between the ages of 21 and 50 who are free of current psychopathology and free of past psychopathology of mood and anxiety disorder, psychotic disorder, and substance drug addiction
- Organic central nervous system disorders
- Able to give consent
- A negative urine toxicology
- For females of child-bearing potential, negative pregnancy urine test
Show all 9Show fewer
- For females child-bearing potential, use of two effective birth control methods for the duration of the study or abstinence.
- Abstinence from ingesting nicotine for at least 6 months before the start of the study.
- See specific criterion for effective birth control methods listed below.
Who cannot join
- Subjects with an unstable medical disorder or a disorder (including surgical interventions) that would likely interfere with the action, absorption, distribution, metabolism or excretion of GSK561679, may pose a safety concern, or interfere with accurate assessment of safety.
- Lifetime or current diagnosis of schizophrenia or other psychotic disorder, mood or anxiety disorder, substance abuse in the last 12 months or lifetime dependence, alcohol abuse in the last 12 months or lifetime dependence. Current Axis I disorder. Clear evidence of a first-degree relative with history of psychosis, bipolar disorder or major depression as determined by the family history interview method; specifically, participant will know diagnosis or treatment in order to confirm presence of disorder.
- 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
- Current evidence or history of significant unstable medical illness or organic brain impairment, including stroke, epilepsy, CNS tumor, demyelinating disease, cardiac, pulmonary, gastrointestinal, renal or hepatic impairment that would likely interfere with the action, absorption, distribution, metabolism, or excretion of GSK561679. Abnormal EKG.
- DSM-IV substance abuse within the past year. Subject has a positive urine test for illegal drug use.
- Diagnosis of anorexia nervosa or bulimia
Show all 23Show fewer
- Subject has a documented history of hepato-biliary disease including a history of, or positive laboratory results for hepatitis (hepatitis B surface antigen and/or hepatitis C antibody), and/or clinically significant hepatic enzyme elevation including any one of the following enzymes greater than 1.5 times the upper limit of normal (ULN) value (ALT, AST, ALP, total or direct bil > 1.5 times the ULN, unless consistent with presumed or diagnosed Gilbert s disease
- Subject has taken systemic corticosteroids within 2 weeks of the Randomization Visit
- All prescription or non-prescription medications and herbal remedies are prohibited within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication and until completion of follow-up procedures, unless in the opinion of the investigator the medication will not interfere with the study procedures or compromise study safety, e.g. rescue medication. As an exception, acetaminophen, no more than 2g/day, and birth control pills are permitted during the study.
- Subject who is likely to require the use of the following medications:
- Chronic (for more than 2 weeks), regular NSAID use unless administered concomitantly with an anti-secretory agent (i.e. proton-pump inhibitor or histamine-2 receptor antagonist)
- Any use of aspirin (including low dose)
- Subject has taken non-psychoactive (prescription or non-prescription), dietary, or herbal products, with a narrow therapeutic index, that are metabolized via the cytochrome P450 3A4 or 2C9 pathway (warfarin), or transported via OATP1B1 or P-gp, within 2 weeks (or 5 half-lives, whichever is longer) prior to the Randomization Visit.
- Subject has taken other (nonpsychoactive) prescription, nonprescription, dietary, or herbal products that are potent inducers or inhibitors of the cytochrome P450 3A4 pathway for 2 weeks (or 5 half lives, whichever is longer) prior to the Randomization Visit.
- Subject has participated in a study with an investigational drug within the period of 30 days prior to screening for this study
- Pregnancy or lactation*
- Subjects who, in the opinion of the investigator, would be noncompliant with the visit schedule or study procedures (e.g. illiteracy, planned vacations, or planned hospitalizations during the study).
- Any laboratory abnormality that in the investigator s judgment is considered to be clinically significant (blood pressure, ECG, TSH, LFT, etc.)
- Previous treatment with CRF1 receptor antagonist
- Allergy to benzodiazepines
- Medical conditions that would influence psychophysiological responses (e.g., cardiovascular disease, previous myocardial infarction, angina, uncontrolled hypertension).
- A history of peptic ulcer disease (PUD)
- A serum pregnancy test is performed during the screening. Since this test might not detect the very early stage of pregnancy (i.e. maximum of 10 day period between fertilization and implantation), women of child-bearing age are excluded from the study if they do not use at least two effective birth control methods for 15 days prior to receiving the study drug. Acceptable methods of birth control include: a double-barrier method (condoms or diaphragm) combined with spermicide; hormonal contraceptives plus single barrier (birth control pills, implants [Norplant] or injections [Depo-Provera]), Intrauterine Device (IUD), or abstinence (no sexual activity).
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Background:
- Research has shown that the hormone corticotropin-releasing hormone (CRH) is involved in stress and anxiety, and that drugs that block the effect of CRH in the body can reduce anxiety. GSK561679 is an experimental drug that attempts to reduce anxiety by blocking the effect of CRH. Researchers are interested in comparing GSK561679 with other treatments for anxiety.
Read more
Objectives:
- To determine the effectiveness of GSK561679 compared with placebo and alprazolam (Xanax), as a possible treatment for fear and anxiety.
Eligibility:
- Healthy female volunteers between 21 and 50 years of age.
Design:
- This study will involve one screening visit, four testing visits, and one follow-up visit over a period of 8-9 weeks. The testing sessions will be between 6-11 days apart.
- Participants must follow these dietary restrictions to participate in the study.
- No nicotine, alcohol, or caffeine (including chocolate and soft drinks) for 24 hours before the start of the study.
- No nicotine in the past 6 months, and no nicotine until the final blood sample is collected at the follow-up visit.
- No alcohol or caffeine for 24 hours before a testing visit or for 72 hours after each visit.
- No grapefruit or grapefruit products from 14 days before the first dose of study medication until collection of the final blood sample.
- Participants will receive a dose of GSK561679, alprazolam, or placebo 3 hours before the testing, and will take an additional pill 1 hour before the testing.
- During the tests, participants will receive brief electric shocks and hear sudden loud noises. The noises and shocks will be given over a period of approximately 40 minutes per session.
- Skin conduction, heart rate, and blinking will be monitored throughout the tests, and participants will be asked about anxiety levels and will be tested on mood, memory, and concentration. Blood and saliva samples will also be taken during these sessions.
- Participants will stay in the clinical center for 1 to 2 hours after the study testing to ensure that the sedation has worn off. Participants will not be allowed to drive home or take public transportation alone after study visits, so alternative transportation must be arranged.
Read the detailed description
Objective: This proposal is a part of an integrated project to test the efficacy of a candidate anxiolytic, a CRF1 receptor antagonist, provided by GlaxoSmithKline (GSK) as part of The Emory-MSSM-GSK-NIMH Collaborative Mood Disorders Initiative, using fear-potentiated startle. The anti-fear and anxiolytic activity of a single dose of the highly specific CRF1 antagonist GSK561679 will be evaluated in healthy female subjects using models of phasic (fear) and sustained (anxiety) aversive states derived from humans and from pre-clinical studies in rodents.
Study population: The study population will consist of 30 healthy female volunteers, 21-50 years of age, and of diverse racial and ethnic backgrounds.
Design: The study will use a double-blind cross-over design in which each subject will receive placebo, Alprazolam (1 mg), and a low (50 mg) and high (400 mg) dose of GSK561679. We will examine the effect of these drugs on the potentiation of startle during anticipation of no-shock, predictable shock signaled by a discrete threat cue, and unpredictable shock.
Outcome measures: The main outcome measures are the magnitude of the startle reflex and retrospective anxiety during each condition. Secondary measures will include the skin conductance response and changes in heart rate, as well as measures of HPA activity.
- Conditions
- Anxiety Disorders
- Keywords
- Treatment, Anxiety, Fear, Fear Potentiated Startle, Healthy Volunteer, HV
- Medical subject headings
- Anxiety Disorders
What is being measured
The primary outcome is the main question the study is designed to answer.
Magnitude of the startle reflex
Measured: One year
Secondary outcomes (1)
Skin conductance response and heart rate
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2010 (estimated)
- Study start22 Jan 2010
- Study completion14 Aug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Anxiety DisordersStudies of the same condition, open and under way.
- More trials run by National Institute of Mental Health (NIMH)The 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
- Observational
- Observational model
- Case crossover
- Time perspective
- Prospective
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Investigators
- Christian Grillon, Ph.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01059227
- Sponsor's protocol ID
- 100049
- Other IDs
- 10-M-0049
- Status last verified
- 14 Aug 2015
- First submitted
- 28 Jan 2010
- Last updated
- 5 Jul 2018
- Results posted
- No
Publications
Baas JM, Grillon C, Bocker KB, Brack AA, Morgan CA 3rd, Kenemans JL, Verbaten MN. Benzodiazepines have no effect on fear-potentiated startle in humans. Psychopharmacology (Berl). 2002 May;161(3):233-47. doi: 10.1007/s00213-002-1011-8. Epub 2002 Mar 20.
PubMed 12021826Barlow DH. Unraveling the mysteries of anxiety and its disorders from the perspective of emotion theory. Am Psychol. 2000 Nov;55(11):1247-63. doi: 10.1037//0003-066x.55.11.1247.
PubMed 11280938Blanchard RJ, Yudko EB, Rodgers RJ, Blanchard DC. Defense system psychopharmacology: an ethological approach to the pharmacology of fear and anxiety. Behav Brain Res. 1993 Dec 20;58(1-2):155-65. doi: 10.1016/0166-4328(93)90100-5.
PubMed 7907880
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of a CRF1 Receptor Antagonist on Human Startle in Normal Female Volunteers
- ClinicalTrials.gov ID
- NCT01059227
- Acronym / sponsor ID
- 100049
- Conditions
- Anxiety Disorders
- Keywords
- Treatment, Anxiety, Fear, Fear Potentiated Startle, Healthy Volunteer, HV
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 22 Jan 2010
- Study completion
- 14 Aug 2015
- First posted
- 29 Jan 2010 (estimated)
- 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.
Background:
- Research has shown that the hormone corticotropin-releasing hormone (CRH) is involved in stress and anxiety, and that drugs that block the effect of CRH in the body can reduce anxiety. GSK561679 is an experimental drug that attempts to reduce anxiety by blocking the effect of CRH. Researchers are interested in comparing GSK561679 with other treatments for anxiety.
Objectives:
- To determine the effectiveness of GSK561679 compared with placebo and alprazolam (Xanax), as a possible treatment for fear and anxiety.
Eligibility:
- Healthy female volunteers between 21 and 50 years of age.
Design:
- This study will involve one screening visit, four testing visits, and one follow-up visit over a period of 8-9 weeks. The testing sessions will be between 6-11 days apart.
- Participants must follow these dietary restrictions to participate in the study.
- No nicotine, alcohol, or caffeine (including chocolate and soft drinks) for 24 hours before the start of the study.
- No nicotine in the past 6 months, and no nicotine until the final blood sample is collected at the follow-up visit.
- No alcohol or caffeine for 24 hours before a testing visit or for 72 hours after each visit.
- No grapefruit or grapefruit products from 14 days before the first dose of study medication until collection of the final blood sample.
- Participants will receive a dose of GSK561679, alprazolam, or placebo 3 hours before the testing, and will take an additional pill 1 hour before the testing.
- During the tests, participants will receive brief electric shocks and hear sudden loud noises. The noises and shocks will be given over a period of approximately 40 minutes per session.
- Skin conduction, heart rate, and blinking will be monitored throughout the tests, and participants will be asked about anxiety levels and will be tested on mood, memory, and concentration. Blood and saliva samples will also be taken during these sessions.
- Participants will stay in the clinical center for 1 to 2 hours after the study testing to ensure that the sedation has worn off. Participants will not be allowed to drive home or take public transportation alone after study visits, so alternative transportation must be arranged.
Detailed description
Objective: This proposal is a part of an integrated project to test the efficacy of a candidate anxiolytic, a CRF1 receptor antagonist, provided by GlaxoSmithKline (GSK) as part of The Emory-MSSM-GSK-NIMH Collaborative Mood Disorders Initiative, using fear-potentiated startle. The anti-fear and anxiolytic activity of a single dose of the highly specific CRF1 antagonist GSK561679 will be evaluated in healthy female subjects using models of phasic (fear) and sustained (anxiety) aversive states derived from humans and from pre-clinical studies in rodents.
Study population: The study population will consist of 30 healthy female volunteers, 21-50 years of age, and of diverse racial and ethnic backgrounds.
Design: The study will use a double-blind cross-over design in which each subject will receive placebo, Alprazolam (1 mg), and a low (50 mg) and high (400 mg) dose of GSK561679. We will examine the effect of these drugs on the potentiation of startle during anticipation of no-shock, predictable shock signaled by a discrete threat cue, and unpredictable shock.
Outcome measures: The main outcome measures are the magnitude of the startle reflex and retrospective anxiety during each condition. Secondary measures will include the skin conductance response and changes in heart rate, as well as measures of HPA activity.
Study design
- Observational model
- Case crossover
- Time perspective
- Prospective
Who may qualify
- Ages
- 21 to 50 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- HEALTHY FEMALE VOLUNTEERS as determined by a responsible physician, based on a medical evaluation including own and familial medical history, physical examination, psychiatric history, psychiatric evaluation, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator agrees that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Females between the ages of 21 and 50 who are free of current psychopathology and free of past psychopathology of mood and anxiety disorder, psychotic disorder, and substance drug addiction
- Organic central nervous system disorders
- Able to give consent
- A negative urine toxicology
Key exclusion criteria (23 listed)
- Subjects with an unstable medical disorder or a disorder (including surgical interventions) that would likely interfere with the action, absorption, distribution, metabolism or excretion of GSK561679, may pose a safety concern, or interfere with accurate assessment of safety.
- Lifetime or current diagnosis of schizophrenia or other psychotic disorder, mood or anxiety disorder, substance abuse in the last 12 months or lifetime dependence, alcohol abuse in the last 12 months or lifetime dependence. Current Axis I disorder. Clear evidence of a first-degree relative with history of psychosis, bipolar disorder or major depression as determined by the family history interview method; specifically, participant will know diagnosis or treatment in order to confirm presence of disorder.
- 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
- Current evidence or history of significant unstable medical illness or organic brain impairment, including stroke, epilepsy, CNS tumor, demyelinating disease, cardiac, pulmonary, gastrointestinal, renal or hepatic impairment that would likely interfere with the action, absorption, distribution, metabolism, or excretion of GSK561679. Abnormal EKG.
- DSM-IV substance abuse within the past year. Subject has a positive urine test for illegal drug use.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Magnitude of the startle reflex
Time frame: One year
1 secondary outcome
Skin conductance response and heart rate
Time frame: One year
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 5 Jul 2018.
- Background: PubMed 12021826Baas JM, Grillon C, Bocker KB, Brack AA, Morgan CA 3rd, Kenemans JL, Verbaten MN. Benzodiazepines have no effect on fear-potentiated startle in humans. Psychopharmacology (Berl). 2002 May;161(3):233-47. doi: 10.1007/s00213-002-1011-8. Epub 2002 Mar 20.
- Background: PubMed 11280938Barlow DH. Unraveling the mysteries of anxiety and its disorders from the perspective of emotion theory. Am Psychol. 2000 Nov;55(11):1247-63. doi: 10.1037//0003-066x.55.11.1247.
- Background: PubMed 7907880Blanchard RJ, Yudko EB, Rodgers RJ, Blanchard DC. Defense system psychopharmacology: an ethological approach to the pharmacology of fear and anxiety. Behav Brain Res. 1993 Dec 20;58(1-2):155-65. doi: 10.1016/0166-4328(93)90100-5.
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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.
Christian Grillon, Ph.D. principal investigator
National Institute of Mental Health (NIMH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Anxiety Disorders, run by National Institute of Mental Health (NIMH) 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 9 inclusion and 23 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 5 Jul 2018. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
Magnitude of the startle reflex (time frame: One year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01059227, which also lists 3 linked publications.
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 5 Jul 2018.