Clinical trial NCT02066792: Dose Timing of D-Cycloserine to Augment CBT for Social Anxiety Disorder
Official title: Dose Timing of D-Cycloserine to Augment CBT for Social Anxiety Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Social Anxiety Disorder
Keywords: Social Phobia
Lead sponsor: University of Texas at Austin
Sponsor class: OTHER
Collaborators: name: Rush University Medical Center
name: Boston University
name: Southern Methodist University
First posted: 2014-02-20
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to examine the efficacy of 50 mg of d-cycloserine in comparison to placebo (a pill containing no medication) for improving the effectiveness of cognitive-behavioral therapy (CBT) in reducing symptoms associated with social anxiety disorder. In addition, the study will examine whether the effectiveness of d-cycloserine depends on the timing of the pill administration (i.e., 1- hour before the session or immediately after the session) as well as the success of the CBT therapy sessions. The investigators hypothesize that the tailored post-session DCS administration condition will outperform the other conditions (pre-session DCS, placebo, and non-tailored post-session DCS). This will be evidenced by short- and long-term improvements in social anxiety severity.


Eligibility criteria: Inclusion Criteria:

* Male or female outpatients \> 18 years of age with a primary psychiatric diagnosis (designated by the patient as the most important source of current distress) of social anxiety disorder as defined by DSM-5 criteria.
* A total score \> 60 on the LSAS.
* Physical examination and laboratory findings without clinically significant abnormalities.
* Willingness and ability to participate in the informed consent process and comply with the requirements of the study protocol.

Exclusion Criteria:

* A lifetime history of bipolar disorder, schizophrenia, psychosis, delusional disorders or obsessive-compulsive disorder; an eating disorder in the past 6 months; organic brain syndrome, mental retardation or other cognitive dysfunction that could interfere with capacity to engage in therapy; a history of substance or alcohol abuse or 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.
* PTSD within the past 6 months. Entry of patients with other mood or anxiety disorders will be permitted if the SAD is judged to be the predominant disorder, in order to increase accrual of a clinically relevant sample. Patients with significant suicidal ideation (MADRS item 10 score \> 3) 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 must be off concurrent psychotropic medication (e.g., antidepressants, anxiolytics, beta blockers) for at least 2 weeks prior to initiation of randomized treatment.
* Significant personality dysfunction likely to interfere with study participation.
* Serious medical illness or instability for which hospitalization may be likely within the next year.
* Patients with a current or past history of seizures.
* Pregnant women, lactating women, and women of childbearing potential who are not using medically accepted forms of contraception (e.g., IUD, oral contraceptives, barrier devices, condoms and foam, or implanted progesterone rods stabilized for at least 3 months).
* Any concurrent psychotherapy initiated within 3 months of baseline, or ongoing psychotherapy of any duration directed specifically toward treatment of the SAD is excluded. Prohibited psychotherapy includes CBT or psychodynamic therapy focusing on exploring specific, dynamic causes of the phobic symptomatology and providing management skills. General supportive therapy initiated \> 3 months prior is acceptable.
* Prior non-response to adequately-delivered exposure (i.e., as defined by the patient's report of receiving specific and regular exposure assignments as part of a previous treatment).
* Patients with a history of head trauma causing loss of consciousness, seizure or ongoing cognitive impairment. Current use of isoniazid or ethionamide compounds
* Insufficient command of the English language

Primary outcomes:
measure: Social Anxiety Symptom Severity
timeFrame: Assessments took place at multiple time points from baseline to 3-month follow-up. The three-month is reported
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Boston
country: United States
facility: Boston University
state: Massachusetts
city: Austin
country: United States
facility: University of Texas at Austin
state: Texas
Study officials:
affiliation: Rush University Medical Center
name: Mark Pollack, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Boston University
name: Stefan Hofmann, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas at Austin
name: Jasper A Smits, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dutcher CD, Dowd SM, Zalta AK, Taylor DJ, Rosenfield D, Perrone A, Otto MW, Pollack MH, Hofmann SG, Smits JAJ. Sleep quality and outcome of exposure therapy in adults with social anxiety disorder. Depress Anxiety. 2021 Nov;38(11):1182-1190. doi: 10.1002/da.23167. Epub 2021 May 19.
citation: Smits JAJ, Pollack MH, Rosenfield D, Otto MW, Dowd S, Carpenter J, Dutcher CD, Lewis EM, Witcraft SM, Papini S, Curtiss J, Andrews L, Kind S, Conroy K, Hofmann SG. Dose Timing of D-Cycloserine to Augment Exposure Therapy for Social Anxiety Disorder: A Randomized Clinical Trial. JAMA Netw Open. 2020 Jun 1;3(6):e206777. doi: 10.1001/jamanetworkopen.2020.6777.
citation: Hofmann SG, Papini S, Carpenter JK, Otto MW, Rosenfield D, Dutcher CD, Dowd S, Lewis M, Witcraft S, Pollack MH, Smits JAJ. Effect of d-cycloserine on fear extinction training in adults with social anxiety disorder. PLoS One. 2019 Oct 17;14(10):e0223729. doi: 10.1371/journal.pone.0223729. eCollection 2019.
citation: Hofmann SG, Carpenter JK, Otto MW, Rosenfield D, Smits JA, Pollack MH. Dose timing of D-cycloserine to augment cognitive behavioral therapy for social anxiety: Study design and rationale. Contemp Clin Trials. 2015 Jul;43:223-30. doi: 10.1016/j.cct.2015.06.015. Epub 2015 Jun 23.