FearNCT00352586
Effect of D-cycloserine on Extinction of Fear Conditioning
An observational study of Fear, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
This study will evaluate whether the drug D-cycloserine (DCS) can improve a type of learning called classical conditioning, in which the brain learns to associate neutral stimuli with stimuli that elicit emotional or physiological responses. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Fear
- How many people
- 160 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Apr 2002to 1 Feb 2008
- 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subjects must meet the following inclusion criteria in order to participate in the study:
- Male or female volunteers ages 18-50 years old.
- Judged to be in good physical health on the basis of medical history and physical examination.
- Able to understand procedures and agree to participate in the study by giving written informed consent.
Who cannot join
- Exclusion criteria will be different for studies with and without (pilot study) DCS. Subjects will be excluded from the DCS study if they meet the following exclusion criteria:
- History of allergy to D-cycloserine (study 1) or nimodipine (study 2).
- No clinically significant organ disease by history, physical examination, LFT's, TFT's, electrolytes, BUN, creatinine, Ca+2, Mg+2, urinalysis, CBC with differential, and EKG.
- History of any disease, which in the investigators' opinion may confound the results of the study, including, but not limited to, history of organic mental disorders, seizure, or mental retardation.
- Any significant medical or neurological problems (e.g. cardiovascular illness, respiratory illness, neurologic illness, seizure, stroke, multiple sclerosis, Alzeimer's disease, etc.)
- Past or current substance dependence.
Show all 12Show fewer
- Presence of psychotropic medications or illicit substance in urine.
- Positive pregnancy test.
- Current or past Axis I psychiatric disorders as identified with the Structured Clinical Interview for DSM-IV-TR axis disorders, non-patient edition (SCID-np).
- Current psychotropic medication.
- Impaired hearing defined as inability to hear a 40 dB(HL) pure tone in the 1000- to 4000 Hz span. Reduced or excessive startle reactivity.
- Neurological symptoms that affect the arms or 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
Official title: Psychopharmacology Investigations of Fear Conditioning in Humans
This study will evaluate whether the drug D-cycloserine (DCS) can improve a type of learning called classical conditioning, in which the brain learns to associate neutral stimuli with stimuli that elicit emotional or physiological responses. DCS is an antibiotic that was initially approved to treat tuberculosis and has been tested in clinical trials over the last decade for enhancing cognitive function. This protocol includes both a pilot study and a main study. The main study will begin after the pilot study ends.
Healthy normal volunteers between 18 and 45 years of age may be eligible for these studies. Candidates will be screened with a medical and psychiatric history and a physical examination that includes blood and urine samples, an electrocardiogram (EKG), hearing test and startle test. The startle test involves recording eyeblink responses to loud noises.
Read more
After the screening visit, those enrolled will participate in the pilot or main study, in which their reactions to two types of stimuli-an unpleasant, but harmless, shock to the arm and a mild puff of air to the eye-will be measured and recorded.
- Pilot Study
Session 1 - Participants will receive very brief electric shocks delivered through two electrodes attached to the forearm or fingers and will hear brief loud sounds that may startle. Geometric shapes will be presented on a computer monitor.
Sessions 2 and 3 - The procedure is the same as in session 1, except participants will also be subjected to brief low-intensity tones and airpuffs to the eye.
- Main Study
Participants will undergo the same procedures described in the pilot study, with the following additions:
- They will have an intravenous tube placed in a vein for collecting blood during the test.
- They will take a pill each test day that contains either 100 mg DCS, 500 mg DCS, or a placebo (inactive substance). Subjects assigned to receive DCS will get the active drug on only one of the three test sessions and will be given placebo the other two sessions. The placebo group will receive placebo all three sessions.
In both the pilot and main study, subjects' physiological responses to the stimuli will be recorded. Electrodes will be placed on two fingers (to measure sweat, or electrodermal activity), on the ribcage midway between the waist and armpit (to measure heart rate), and under one eye (to measure eye blink). Pulse will be recorded with a device attached to a finger, and breathing rate will be recorded with a special belt placed around the chest. At various times during the sessions, subjects will fill out questionnaires about their experience. Participants may withdraw from the study at any point.
Read the detailed description
This protocol examines the effect of two drugs on fear conditioning. Study 1 tests assess whether D-cycloserine (DCS) facilitates extinction of fear conditioning and acquisition of eyeblink conditioning. Study 2 examines whether the calcium channel blocker nimodipine blocks acquisition of fear conditioning and eyeblink conditioning.
Study 1: The demonstration that activation of NMDA receptors is necessary for long-term potentiation suggests that this subclass of amino acid may be involved in certain types of learning and memory. The present project will examine the effect DCS, a partial agonist at the glycine modulatory site on the NMDA receptor, on two associative learning tasks, extinction of fear conditioning and acquisition of eyeblink conditioning. The inability to extinguish intense fear memories is a significant clinical problem. Finding procedures or treatments that facilitate extinction of fear memories is of paramount importance. In animals, extinction of conditioned fear involves an active learning process that is blocked by NMDA antagonists. Recently, Dr. Michael Davis (Emory University) demonstrated that the administration of DCS prior to extinction produces a dose-dependent facilitation of extinction of conditioned fear in the rat, when assessed with fear-potentiated startle. We propose to examine whether the clinically important process of extinction can also be enhanced by DCS in humans. Another aim of the study is to examine whether DCS facilitates a hippocampal-mediated task, trace eyeblink conditioning. The hippocampus is particularly rich in NMDA receptors and DCS blocks trace eyeblink conditioning in the rabbit. The present study will examine the effect of placebo, 100 mg DCS, and 500 mg DCS on extinction, retention, and reinstatement of fear-potentiated startle conditioning and acquisition of trace eyeblink conditioning. The first experimental session (acquisition) will be a fear conditioning procedure (paired presentation of a conditioned stimulus or CS and a mildly unpleasant shock). During the second experimental session (extinction), DCS or placebo will be given to the subjects 1 hour prior to an extinction procedure (CS presented without shock). Following extinction, the eyeblink conditioning study will be conducted. Finally, in the third experimental session, retention of fear and eyeblink conditioning will be evaluated. We hypothesized that compared to placebo, DCS will speed up learning, i.e., it will facilitate extinction of fear conditioning and acquisition of eyeblink conditioning.
Study 2: The rationale for testing nimodipine is highly similar to the rationale for testing DCS, and the procedure is very similar. Understanding the neurochemical bases of fear acquisition and fear extinction may provide insights into pathological anxiety and help develop more effective treatments. This study will be conducted over two experimental sessions (and a screening session). Nimodipine or placebo will be given during the 1st session prior to acquisition of fear conditioning and eyeblink conditioning. The 2nd session will be a test of retention of eyeblink conditioning. We hypothesized that nimodipine will impair fear conditioning and eyeblink conditioning.
- Conditions
- Fear
- Keywords
- Classical Conditioning, Learning, NMDA, Startle, Eyeblink, Anxiety, Fear Conditioning, Fear Potentiated Startle, Extinction, D-cycloserine, Healthy Volunteer, HV, Normal Control
- 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 posted14 Jul 2006 (estimated)
- Study start3 Apr 2002
- Study completion1 Feb 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for FearStudies 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
- 160 participants
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00352586
- Sponsor's protocol ID
- 020157
- Other IDs
- 02-M-0157
- Status last verified
- 1 Feb 2008
- First submitted
- 13 Jul 2006
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Gorman JM, Kent JM, Sullivan GM, Coplan JD. Neuroanatomical hypothesis of panic disorder, revised. Am J Psychiatry. 2000 Apr;157(4):493-505. doi: 10.1176/appi.ajp.157.4.493.
PubMed 10739407
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Psychopharmacology Investigations of Fear Conditioning in Humans
- ClinicalTrials.gov ID
- NCT00352586
- Acronym / sponsor ID
- 020157
- Conditions
- Fear
- Keywords
- Classical Conditioning, Learning, NMDA, Startle, Eyeblink, Anxiety, Fear Conditioning, Fear Potentiated Startle
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 160 participants
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 3 Apr 2002
- Study completion
- 1 Feb 2008
- First posted
- 14 Jul 2006 (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.
This study will evaluate whether the drug D-cycloserine (DCS) can improve a type of learning called classical conditioning, in which the brain learns to associate neutral stimuli with stimuli that elicit emotional or physiological responses. DCS is an antibiotic that was initially approved to treat tuberculosis and has been tested in clinical trials over the last decade for enhancing cognitive function. This protocol includes both a pilot study and a main study. The main study will begin after the pilot study ends.
Healthy normal volunteers between 18 and 45 years of age may be eligible for these studies. Candidates will be screened with a medical and psychiatric history and a physical examination that includes blood and urine samples, an electrocardiogram (EKG), hearing test and startle test. The startle test involves recording eyeblink responses to loud noises.
After the screening visit, those enrolled will participate in the pilot or main study, in which their reactions to two types of stimuli-an unpleasant, but harmless, shock to the arm and a mild puff of air to the eye-will be measured and recorded.
- Pilot Study
Session 1 - Participants will receive very brief electric shocks delivered through two electrodes attached to the forearm or fingers and will hear brief loud sounds that may startle. Geometric shapes will be presented on a computer monitor.
Sessions 2 and 3 - The procedure is the same as in session 1, except participants will also be subjected to brief low-intensity tones and airpuffs to the eye.
- Main Study
Participants will undergo the same procedures described in the pilot study, with the following additions:
- They will have an intravenous tube placed in a vein for collecting blood during the test.
- They will take a pill each test day that contains either 100 mg DCS, 500 mg DCS, or a placebo (inactive substance). Subjects assigned to receive DCS will get the active drug on only one of the three test sessions and will be given placebo the other two sessions. The placebo group will receive placebo all three sessions.
In both the pilot and main study, subjects' physiological responses to the stimuli will be recorded. Electrodes will be placed on two fingers (to measure sweat, or electrodermal activity), on the ribcage midway between the waist and armpit (to measure heart rate), and under one eye (to measure eye blink). Pulse will be recorded with a device attached to a finger, and breathing rate will be recorded with a special belt placed around the chest. At various times during the sessions, subjects will fill out questionnaires about their experience. Participants may withdraw from the study at any point.
Detailed description
This protocol examines the effect of two drugs on fear conditioning. Study 1 tests assess whether D-cycloserine (DCS) facilitates extinction of fear conditioning and acquisition of eyeblink conditioning. Study 2 examines whether the calcium channel blocker nimodipine blocks acquisition of fear conditioning and eyeblink conditioning.
Study 1: The demonstration that activation of NMDA receptors is necessary for long-term potentiation suggests that this subclass of amino acid may be involved in certain types of learning and memory. The present project will examine the effect DCS, a partial agonist at the glycine modulatory site on the NMDA receptor, on two associative learning tasks, extinction of fear conditioning and acquisition of eyeblink conditioning. The inability to extinguish intense fear memories is a significant clinical problem. Finding procedures or treatments that facilitate extinction of fear memories is of paramount importance. In animals, extinction of conditioned fear involves an active learning process that is blocked by NMDA antagonists. Recently, Dr. Michael Davis (Emory University) demonstrated that the administration of DCS prior to extinction produces a dose-dependent facilitation of extinction of conditioned fear in the rat, when assessed with fear-potentiated startle. We propose to examine whether the clinically important process of extinction can also be enhanced by DCS in humans. Another aim of the study is to examine whether DCS facilitates a hippocampal-mediated task, trace eyeblink conditioning. The hippocampus is particularly rich in NMDA receptors and DCS blocks trace eyeblink conditioning in the rabbit. The present study will examine the effect of placebo, 100 mg DCS, and 500 mg DCS on extinction, retention, and reinstatement of fear-potentiated startle conditioning and acquisition of trace eyeblink conditioning. The first experimental session (acquisition) will be a fear conditioning procedure (paired presentation of a conditioned stimulus or CS and a mildly unpleasant shock). During the second experimental session (extinction), DCS or placebo will be given to the subjects 1 hour prior to an extinction procedure (CS presented without shock). Following extinction, the eyeblink conditioning study will be conducted. Finally, in the third experimental session, retention of fear and eyeblink conditioning will be evaluated. We hypothesized that compared to placebo, DCS will speed up learning, i.e., it will facilitate extinction of fear conditioning and acquisition of eyeblink conditioning.
Study 2: The rationale for testing nimodipine is highly similar to the rationale for testing DCS, and the procedure is very similar. Understanding the neurochemical bases of fear acquisition and fear extinction may provide insights into pathological anxiety and help develop more effective treatments. This study will be conducted over two experimental sessions (and a screening session). Nimodipine or placebo will be given during the 1st session prior to acquisition of fear conditioning and eyeblink conditioning. The 2nd session will be a test of retention of eyeblink conditioning. We hypothesized that nimodipine will impair fear conditioning and eyeblink conditioning.
Study design
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Male or female volunteers ages 18-50 years old.
- Judged to be in good physical health on the basis of medical history and physical examination.
- Able to understand procedures and agree to participate in the study by giving written informed consent.
Key exclusion criteria (12 listed)
- Exclusion criteria will be different for studies with and without (pilot study) DCS. Subjects will be excluded from the DCS study if they meet the following exclusion criteria:
- History of allergy to D-cycloserine (study 1) or nimodipine (study 2).
- No clinically significant organ disease by history, physical examination, LFT's, TFT's, electrolytes, BUN, creatinine, Ca+2, Mg+2, urinalysis, CBC with differential, and EKG.
- History of any disease, which in the investigators' opinion may confound the results of the study, including, but not limited to, history of organic mental disorders, seizure, or mental retardation.
- Any significant medical or neurological problems (e.g. cardiovascular illness, respiratory illness, neurologic illness, seizure, stroke, multiple sclerosis, Alzeimer's disease, etc.)
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 2 Jul 2017.
- Background: PubMed 10739407Gorman JM, Kent JM, Sullivan GM, Coplan JD. Neuroanatomical hypothesis of panic disorder, revised. Am J Psychiatry. 2000 Apr;157(4):493-505. doi: 10.1176/appi.ajp.157.4.493.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Fear, 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 4 inclusion and 12 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 2 Jul 2017. 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 NCT00352586, which also lists 1 linked publication.
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 2 Jul 2017.