Stress Disorders, Posttraumatic
Conditions
Keywords
Stress Disorders, Posttraumatic, Hydrocortisone, Cycloserine, Extinction, Psychological, PTSD, San Francisco
Brief summary
This is a research study examining the use of two medications, Hydrocortisone and D-Cycloserine, compared to an inactive substance (placebo), on their ability to reduce fear responses and memory of fear in Veterans with symptoms of Posttraumatic Stress Disorder (PTSD). These responses will be tested using a fear learning and memory task administered by computer.
Interventions
DRUGHydrocortisone
25 mg/oral one hour prior to extinction task
DRUGD-Cycloserine
50 mg/oral one hour prior to extinction task
DRUGPlacebo
One hour prior to extinction task
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Veterans and civilians with an age range of 18 to 65 years * Participants must be physically healthy volunteers
Exclusion criteria
* Individuals who fall outside the age range * Individuals with medical conditions that would interfere with participation * Other criteria
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Maximum Skin Conductance Response (SCR) in Microsiemens (µS) | 15 minute measurement intervals on Study Days 7, 9, and 16 | Psychophysiology measurements occurred on day 7 for fear conditioning, day 9 for fear extinction, and day 11 for extinction retention. The primary outcome measures are presented for the first and last conditioned stimulus (CS) trials during fear conditioning and extinction and for the first 2 trials during retention. Conditioned Responses (CR): An SCR score was obtained for each CS by subtracting the mean skin conductance level (SCL) in microsiemens (µS) for the 2-s interval immediately preceding CS onset from the max SC level in µS during the 8-s CS presentation. Unconditioned Response (UCR): An SCR score for the UCR was obtained by subtracting the mean SCL in µS within 6-8 s following CS offset from the max increase in SC level during the .5-6.5 time interval following the CS offset, corresponding to the onset of the .5s US. SC responses were range corrected using each participant's maximum response to the UCS or CS during acquisition trials of the fear conditioning phase. |
Countries
United States
Participant flow
Pre-assignment details
Participation involved 4 study visits, with randomization to intervention arm and drug administration occurring on visit 3. The discrepancy between 111 participants who were initially enrolled and 106 at randomization resulted from 5 participants who dropped out between screening and visit 3, when they were to have been assigned into a group.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: Hydrocortisone Hydrocortisone
Hydrocortisone: 25 mg/oral one hour prior to extinction task | 37 |
| Arm 2: D-Cycloserine D-Cycloserine
D-Cycloserine: 50 mg/oral one hour prior to extinction task | 34 |
| Arm 3: Placebo Placebo
Placebo: One hour prior to extinction task | 35 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Arm 1: Hydrocortisone | Total | Arm 3: Placebo | Arm 2: D-Cycloserine |
|---|---|---|---|---|
| Age, Continuous | 36.0 years STANDARD_DEVIATION 12.8 | 38.6 years STANDARD_DEVIATION 12.6 | 40.0 years STANDARD_DEVIATION 11.8 | 41.1 years STANDARD_DEVIATION 13.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 18 Participants | 7 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants | 88 Participants | 28 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 8 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 18 Participants | 7 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 7 Participants | 12 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 22 Participants | 68 Participants | 25 Participants | 21 Participants |
| Region of Enrollment United States | 37 Participants | 106 Participants | 35 Participants | 34 Participants |
| Sex: Female, Male Female | 23 Participants | 62 Participants | 18 Participants | 21 Participants |
| Sex: Female, Male Male | 14 Participants | 44 Participants | 17 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 37 | 0 / 32 | 0 / 35 |
| other Total, other adverse events | 0 / 37 | 0 / 32 | 0 / 35 |
| serious Total, serious adverse events | 0 / 37 | 0 / 32 | 0 / 35 |
Outcome results
Primary
Proportion of Maximum Skin Conductance Response (SCR) in Microsiemens (µS)
Psychophysiology measurements occurred on day 7 for fear conditioning, day 9 for fear extinction, and day 11 for extinction retention. The primary outcome measures are presented for the first and last conditioned stimulus (CS) trials during fear conditioning and extinction and for the first 2 trials during retention. Conditioned Responses (CR): An SCR score was obtained for each CS by subtracting the mean skin conductance level (SCL) in microsiemens (µS) for the 2-s interval immediately preceding CS onset from the max SC level in µS during the 8-s CS presentation. Unconditioned Response (UCR): An SCR score for the UCR was obtained by subtracting the mean SCL in µS within 6-8 s following CS offset from the max increase in SC level during the .5-6.5 time interval following the CS offset, corresponding to the onset of the .5s US. SC responses were range corrected using each participant's maximum response to the UCS or CS during acquisition trials of the fear conditioning phase.
Time frame: 15 minute measurement intervals on Study Days 7, 9, and 16
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1: Hydrocortisone | Proportion of Maximum Skin Conductance Response (SCR) in Microsiemens (µS) | Fear Extinction: End | .0013351 proportion of max SCR (µS) | Standard Error 0.0313355 |
| Arm 1: Hydrocortisone | Proportion of Maximum Skin Conductance Response (SCR) in Microsiemens (µS) | Fear Extinction: Beginning | .0298132 proportion of max SCR (µS) | Standard Error 0.0313355 |
| Arm 1: Hydrocortisone | Proportion of Maximum Skin Conductance Response (SCR) in Microsiemens (µS) | Fear Conditioning: Beginning | .0325522 proportion of max SCR (µS) | Standard Error 0.0351212 |
| Arm 1: Hydrocortisone | Proportion of Maximum Skin Conductance Response (SCR) in Microsiemens (µS) | Fear Conditioning: End | .1233174 proportion of max SCR (µS) | Standard Error 0.0351212 |
| Arm 1: Hydrocortisone | Proportion of Maximum Skin Conductance Response (SCR) in Microsiemens (µS) | Extinction Retention | -.0101856 proportion of max SCR (µS) | Standard Error 0.0388043 |
| Arm 2: D-Cycloserine | Proportion of Maximum Skin Conductance Response (SCR) in Microsiemens (µS) | Fear Extinction: Beginning | .0674658 proportion of max SCR (µS) | Standard Error 0.0327715 |
| Arm 2: D-Cycloserine | Proportion of Maximum Skin Conductance Response (SCR) in Microsiemens (µS) | Fear Conditioning: Beginning | .0245775 proportion of max SCR (µS) | Standard Error 0.0367306 |
| Arm 2: D-Cycloserine | Proportion of Maximum Skin Conductance Response (SCR) in Microsiemens (µS) | Fear Conditioning: End | .1024914 proportion of max SCR (µS) | Standard Error 0.0367306 |
| Arm 2: D-Cycloserine | Proportion of Maximum Skin Conductance Response (SCR) in Microsiemens (µS) | Fear Extinction: End | -.026853 proportion of max SCR (µS) | Standard Error 0.0327715 |
| Arm 2: D-Cycloserine | Proportion of Maximum Skin Conductance Response (SCR) in Microsiemens (µS) | Extinction Retention | -.0248148 proportion of max SCR (µS) | Standard Error 0.0405825 |
| Arm 3: Placebo | Proportion of Maximum Skin Conductance Response (SCR) in Microsiemens (µS) | Extinction Retention | .0985292 proportion of max SCR (µS) | Standard Error 0.0393708 |
| Arm 3: Placebo | Proportion of Maximum Skin Conductance Response (SCR) in Microsiemens (µS) | Fear Extinction: End | .0854075 proportion of max SCR (µS) | Standard Error 0.0313355 |
| Arm 3: Placebo | Proportion of Maximum Skin Conductance Response (SCR) in Microsiemens (µS) | Fear Conditioning: Beginning | -.0181339 proportion of max SCR (µS) | Standard Error 0.0328529 |
| Arm 3: Placebo | Proportion of Maximum Skin Conductance Response (SCR) in Microsiemens (µS) | Fear Extinction: Beginning | .1104578 proportion of max SCR (µS) | Standard Error 0.0313355 |
| Arm 3: Placebo | Proportion of Maximum Skin Conductance Response (SCR) in Microsiemens (µS) | Fear Conditioning: End | .1276977 proportion of max SCR (µS) | Standard Error 0.0328529 |
Comparison: Fear Conditioning Beginning (first trial)p-value: =0.6695% CI: [-0.15, 0.1]Mixed Models Analysis
Comparison: Fear Conditioning Beginning (first trial)p-value: =0.4195% CI: [-0.17, 0.07]Mixed Models Analysis
Comparison: Fear Conditioning End (last trial)p-value: =0.4395% CI: [-0.07, 0.18]Mixed Models Analysis
Comparison: Fear Conditioning End (last trial)p-value: =0.4795% CI: [-0.07, 0.17]Mixed Models Analysis
Comparison: Fear Extinction Beginning (first trial)p-value: =0.06595% CI: [-0.01, 0.2]Mixed Models Analysis
Comparison: Fear Extinction Beginning (first trial)p-value: =0.3495% CI: [-0.05, 0.15]Mixed Models Analysis
Comparison: Extinction End (last trial)p-value: =0.00395% CI: [0.06, 0.26]Mixed Models Analysis
Comparison: Extinction End (last trial)p-value: 0.0295% CI: [0.02, 0.22]Mixed Models Analysis
Comparison: Extinction Retention (first 2 trials) First trials were selected as a test of extinction retention, since repeated presentations of the CS without a UCS were expected to result in additional fear extinction.p-value: =0.00695% CI: [0.05, 0.3]Mixed Models Analysis
Comparison: Extinction retentionp-value: =0.0195% CI: [0.04, 0.28]Mixed Models Analysis