HealthyNCT00044096
Psychopharmacology of Fear-Potentiated Startle in Humans
An observational study of Healthy, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
The purpose of this study is to understand the effects of the drug alprazolam (Xanax ) on anxiety. To understand the effect of anxiety-relieving drugs on fear and anxiety, researchers often have participants anticipate unpleasant stimuli. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- How many people
- 225 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Aug 2002to 17 Sep 2013
- 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 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subjects will be healthy volunteers between 18-45 years old and free of current psychopathology and organic central nervous system disorders.
Who cannot join
- Any significant medical or neurological problems (e.g. cardiovascular illness, respiratory illness, neurologic illness, seizure, etc.)
- Adverse reactions to cortisol (cortisol study only)
- Adverse reactions to benzodiazepines or antihistamines (alprazolam study only)
- History of angioedema
- Osteoporosis (Hydrocortisone study only)
- High or low blood pressure
Show all 19Show fewer
- History of fainting
- First degree relative with history of mania, schizophrenia, or other psychoses
- A history of mania, schizophrenia, or other psychoses
- Current migraine
- Use of herbal medicines or dietary supplements with psychoactive properties (citalopram study only)
- Any current psychiatric disorders
- Past alcohol/drug dependence and alcohol/drug abuse in past one year
- Current use of psychotropic medication
- Impaired hearing
- Pregnancy
- Breast-feeding or currently taking contraceptive hormones (oxytocin/vasopressin study only)
- Positive results of beta-human chorionic gonadotropin testing (females only)
- Neurological syndrome of the wrist (e.g., carpal tunnel syndrome)
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
The purpose of this study is to understand the effects of the drug alprazolam (Xanax ) on anxiety.
To understand the effect of anxiety-relieving drugs on fear and anxiety, researchers often have participants anticipate unpleasant stimuli. Anticipating unpleasant stimuli increases or potentiates a simple reflex called the startle reflex. The so-called fear-potentiated startle reflex (FPS) effect may be blocked or reduced by anxiety-relieving drugs. Evidence suggests that the FPS can be mediated by two mechanisms that regulate the phasic- and sustained enhancement of startle. This study will elicit phasic and sustained FPS in participants by having them anticipate moderately painful stimuli that are administered predictably and unpredictably. The main goal of this study is to assess the affect of alprazolam on the phasic and sustained enhancement of startle.
This study comprises two pilot experiments and a main study. Participants in the study will be screened with a psychiatric history, physical examination, electrocardiogram (EKG), and blood and urine tests. Participants will four testing sessions separated by 5 to 10 days. At each session, participants will be given one of two doses of alprazolam, diphenhydramine, or placebo (an inactive pill). Questionnaires and other tests will be performed.
Read the detailed description
Objective:
Recent breakthroughs in biomedical research have not improved the ability to identify successful pharmacological treatments derived from novel candidate compounds. This is partly due to the inability of the existing scientific approach to translate candidate anxiolytics identified through the drug discovery process into efficient psychopharmacological treatment of patients. A new drug development approach urgently needs to be implemented to improve predictability and efficiency in translating the basic science explosion into validated drug targets. A key approach to improve the selection of candidate anxiolytics for clinical trials is to fill the gap between animal models and clinical studies in patients by implementing tests in healthy humans with a predictive validity of subsequent clinical efficacy. As a step towards this goal, we developed integrative experimental models of fear and anxiety in non-clinical subjects. We now use these models to identify the anxiolytic and anxiogenic properties of various compounds. The current specific objectives are to 1) further test the psychopharmacological validity of the model using recognized anxiolytics (the SSRI citalopram), 2) test the properties of compounds that are hypothesized to be anxiolytic or anxiogenic (e.g., oxytocin, arginine vasopressin, hydrocortisone) and 3) examine the time course of the anxiolytic effect of the benzodiazepine alprazolam on FPS.
Study population:
Medically and psychiatrically healthy males and females ages 18 to 45.
Design:
The study examines fear and anxiety elicited by unpleasant electric shock delivered predictably and unpredictably, respectively. The following drugs will be tested:
- Citalopram, 2) oxytocin and arginine vasopressin, 3) hydrocortisone, 4) alprazolam.
Outcome measures:
The primary outcome measure is the startle reflex. Secondary measures include the skin conductance response, the heart rate, and subjective measures of anxiety.
- Conditions
- Healthy
- Keywords
- SSRI, Anxiety, Stress, Citalopram, Benadryl, Diphenhydramine, Startle, Fear-Potentiated Startle, Fear, Normal Volunteers, Healthy Volunteers, HV
- Medical subject headings
- Anxiety Disorders
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2002 (estimated)
- Study start15 Aug 2002
- Study completion17 Sep 2013
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 HealthyStudies 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
- Enrolment
- 225 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
- NCT00044096
- Sponsor's protocol ID
- 020263
- Other IDs
- 02-M-0263
- Status last verified
- 17 Sep 2013
- First submitted
- 16 Aug 2002
- Last updated
- 5 Jul 2018
- Results posted
- No
Publications
Bitsios P, Philpott A, Langley RW, Bradshaw CM, Szabadi E. Comparison of the effects of diazepam on the fear-potentiated startle reflex and the fear-inhibited light reflex in man. J Psychopharmacol. 1999;13(3):226-34. doi: 10.1177/026988119901300303.
PubMed 10512076Riba J, Rodriguez-Fornells A, Urbano G, Morte A, Antonijoan R, Barbanoj MJ. Differential effects of alprazolam on the baseline and fear-potentiated startle reflex in humans: a dose-response study. Psychopharmacology (Berl). 2001 Oct;157(4):358-67. doi: 10.1007/s002130100816.
PubMed 11605094Davis M, Falls WA, Campeau S, Kim M. Fear-potentiated startle: a neural and pharmacological analysis. Behav Brain Res. 1993 Dec 20;58(1-2):175-98. doi: 10.1016/0166-4328(93)90102-v.
PubMed 8136044
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
- Psychopharmacology of Fear-Potentiated Startle in Humans
- ClinicalTrials.gov ID
- NCT00044096
- Acronym / sponsor ID
- 020263
- Conditions
- Healthy
- Keywords
- SSRI, Anxiety, Stress, Citalopram, Benadryl, Diphenhydramine, Startle, Fear-Potentiated Startle
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 225 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 15 Aug 2002
- Study completion
- 17 Sep 2013
- First posted
- 19 Aug 2002 (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.
The purpose of this study is to understand the effects of the drug alprazolam (Xanax ) on anxiety.
To understand the effect of anxiety-relieving drugs on fear and anxiety, researchers often have participants anticipate unpleasant stimuli. Anticipating unpleasant stimuli increases or potentiates a simple reflex called the startle reflex. The so-called fear-potentiated startle reflex (FPS) effect may be blocked or reduced by anxiety-relieving drugs. Evidence suggests that the FPS can be mediated by two mechanisms that regulate the phasic- and sustained enhancement of startle. This study will elicit phasic and sustained FPS in participants by having them anticipate moderately painful stimuli that are administered predictably and unpredictably. The main goal of this study is to assess the affect of alprazolam on the phasic and sustained enhancement of startle.
This study comprises two pilot experiments and a main study. Participants in the study will be screened with a psychiatric history, physical examination, electrocardiogram (EKG), and blood and urine tests. Participants will four testing sessions separated by 5 to 10 days. At each session, participants will be given one of two doses of alprazolam, diphenhydramine, or placebo (an inactive pill). Questionnaires and other tests will be performed.
Detailed description
Objective:
Recent breakthroughs in biomedical research have not improved the ability to identify successful pharmacological treatments derived from novel candidate compounds. This is partly due to the inability of the existing scientific approach to translate candidate anxiolytics identified through the drug discovery process into efficient psychopharmacological treatment of patients. A new drug development approach urgently needs to be implemented to improve predictability and efficiency in translating the basic science explosion into validated drug targets. A key approach to improve the selection of candidate anxiolytics for clinical trials is to fill the gap between animal models and clinical studies in patients by implementing tests in healthy humans with a predictive validity of subsequent clinical efficacy. As a step towards this goal, we developed integrative experimental models of fear and anxiety in non-clinical subjects. We now use these models to identify the anxiolytic and anxiogenic properties of various compounds. The current specific objectives are to 1) further test the psychopharmacological validity of the model using recognized anxiolytics (the SSRI citalopram), 2) test the properties of compounds that are hypothesized to be anxiolytic or anxiogenic (e.g., oxytocin, arginine vasopressin, hydrocortisone) and 3) examine the time course of the anxiolytic effect of the benzodiazepine alprazolam on FPS.
Study population:
Medically and psychiatrically healthy males and females ages 18 to 45.
Design:
The study examines fear and anxiety elicited by unpleasant electric shock delivered predictably and unpredictably, respectively. The following drugs will be tested:
- Citalopram, 2) oxytocin and arginine vasopressin, 3) hydrocortisone, 4) alprazolam.
Outcome measures:
The primary outcome measure is the startle reflex. Secondary measures include the skin conductance response, the heart rate, and subjective measures of anxiety.
Study design
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Subjects will be healthy volunteers between 18-45 years old and free of current psychopathology and organic central nervous system disorders.
Key exclusion criteria (19 listed)
- Any significant medical or neurological problems (e.g. cardiovascular illness, respiratory illness, neurologic illness, seizure, etc.)
- Adverse reactions to cortisol (cortisol study only)
- Adverse reactions to benzodiazepines or antihistamines (alprazolam study only)
- History of angioedema
- Osteoporosis (Hydrocortisone study only)
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
Not reported in the source record.
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 10512076Bitsios P, Philpott A, Langley RW, Bradshaw CM, Szabadi E. Comparison of the effects of diazepam on the fear-potentiated startle reflex and the fear-inhibited light reflex in man. J Psychopharmacol. 1999;13(3):226-34. doi: 10.1177/026988119901300303.
- Background: PubMed 11605094Riba J, Rodriguez-Fornells A, Urbano G, Morte A, Antonijoan R, Barbanoj MJ. Differential effects of alprazolam on the baseline and fear-potentiated startle reflex in humans: a dose-response study. Psychopharmacology (Berl). 2001 Oct;157(4):358-67. doi: 10.1007/s002130100816.
- Background: PubMed 8136044Davis M, Falls WA, Campeau S, Kim M. Fear-potentiated startle: a neural and pharmacological analysis. Behav Brain Res. 1993 Dec 20;58(1-2):175-98. doi: 10.1016/0166-4328(93)90102-v.
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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 Healthy, 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 1 inclusion and 19 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00044096, 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.