Effects of a CRF1 Receptor Antagonist on Human Startle in Normal Female Volunteers
Condition: Anxiety Disorders
MeSH terms: Anxiety Disorders
Study type: Observational

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. 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.
    

Observational model: Case-Crossover
Time perspective: Prospective
Keywords: Treatment; Anxiety; Fear; Fear Potentiated Startle; Healthy Volunteer; HV