Effect of D-cycloserine on a Short Imagery Rescripting Intervention for Subclinical PTSD

The primary aim of this proof-of-concept-study is to investigate the utility of d-cycloserine
(DCS; a partial N-methyl-D-aspartate receptor agonist) for enhancing the effect of a novel
psychosocial intervention, imagery rescripting (ImRs).

ImRs is a therapeutic technique that has shown positive outcomes for people suffering from
PTSD and as an adjunct to CBT for PTSD. Patients are asked to recall their memory of a
specific traumatic experience, and then to imagine an intervention that changes the course
and outcome of the event to produce a more satisfying result. It is hypothesized that
reconsolidation of the trauma memory is the mechanism of ImRs. DCS augments exposure therapy
but also appears to enhance reconsolidation of memory. We hypothesize that DCS will enhance
the effect of ImRs by incorporating safety cues into the trauma memory.

Sixty adults with PTSD symptoms due to a traumatic event at least three months prior to
intake will receive 4 sessions of either: CBT + ImRs, or CBT + imaginal exposure (IE). In
sessions 2 and 3, participants will be randomized to receive either DCS or placebo (PLA).

We hypothesize that DCS + ImRs sessions will enhance treatment outcome by facilitating
reconsolidation of the trauma memories incorporating new safety cues. We also hypothesize
that ImRs + PLA will provide equal or better outcomes as the IE + PLA condition.

The primary outcome measure will be improvements in PTSD symptoms, as assessed at baseline,
post-treatment and at 1-month follow-up. Secondary outcome measures will be self-report
questionnaires assessing depression symptoms, general psychological complaints, sleep
quality, quality of life, and PTSD cognitions.

Inclusion Criteria:

- Adult outpatients ≥ 18 years of age, who have experienced a traumatic event such as
sexual assault, physical assualt, a serious accident, or other event where they feared
for their life or their safety, at least 3 months prior to intake, with a primary
subclinical psychiatric diagnosis of post-traumatic stress disorder (PTSD) as measured
by the CAPS-5 (structured clinical interview to assess for PTSD according to the
DSM-5). Eligible participants will have a CAPS-5 score of mild or moderate.

- Physical examination and laboratory findings within normal limits, as determined by
the study nurse.

- Willingness and ability to participate in the informed consent process and comply with
the requirements of the study protocol.

- Potential subjects must have sufficient command of the English language.

Exclusion Criteria:

- A lifetime history of bipolar disorder, schizophrenia, psychosis, delusional disorders
or organic brain syndrome; past history of reported or current seizures; use of
Isoniazid (a particular antibiotic); cognitive dysfunction that can interfere with
capacity to engage in therapy;

- A history of substance or alcohol dependence (other than nicotine) in the last 6
months (or otherwise unable to commit to refraining from alcohol use during the acute
period of study participation). The acute period of study participation is defined as
during their visit and 24 hours before and after their visit.

- Patients with significant suicidal ideation or who have enacted suicidal behaviors
within 6 months prior to intake will be excluded from study participation and referred
for appropriate clinical intervention.

- Patients cannot be taking psychotropic medication during the study period. They have
to be off psychotropic medication for three weeks.

- Participating in ongoing exposure-based psychotherapy for PTSD or psychodynamic
therapy focusing on exploring specific, dynamic causes of the traumatic symptomatology
and providing management skills. General supportive therapy initiated > 3 months prior
to study is acceptable.

- Significant personality dysfunction likely to interfere with study participation. For
example, overly aggressive behavior or disruptive behavior that might jeopardize
safety of the staff or impairs providing the treatment.

- Serious medical illness or instability for which hospitalization may be likely within
the next year. For example, if people are currently in a treatment for cancer, or
people that are waiting for organ donation. This decision would be determined by our
medical staff during the eligibility screen.

- Patients with a current or past history of epilepsy or seizures.

- Patients who have experienced any cardiac event. Patients with clinically significant
abnormalities in vital signs (e.g., systolic blood pressure >150 mm Hg or diastolic
blood pressure >100 mm Hg) at screening will be excluded from further study
participation and referred for appropriate clinical management.

- Pregnant women, lactating women, women who are breastfeeding and women of childbearing
potential who are not using medically accepted forms of contraception (e.g., IUD, oral
contraceptives, or implanted progesterone rods stabilized for at least 3 months).

- Patients with a history of head trauma causing loss of consciousness, or ongoing
cognitive impairment.

- Patients who experienced multiple events of interpersonal trauma prior to the age of
14.