Ignite Creation Date:
2024-05-05 @ 4:56 PM
Last Modification Date:
2024-10-26 @ 9:26 AM
Study NCT ID:
NCT00352586
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2006-07-13
Brief Title:
Effect of D-cycloserine on Extinction of Fear Conditioning
Sponsor:
National Institute of Mental Health NIMH
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Psychopharmacology Investigations of Fear Conditioning in Humans
Status:
COMPLETED
Status Verified Date:
2008-02-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 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
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 ie 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 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 ie 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 02-M-0157 | None | None | None |