Phobic DisordersPhase 2NCT00128401
Use of an Antibiotic as an Enhancer for the Treatment of Social Phobia
A Phase 2 study testing D-Cycloserine in people with Phobic Disorders and Anxiety, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
This study examines whether an antibiotic, d-cycloserine (DCS), boosts the effectiveness of cognitive behavior therapy (CBT) for social anxiety. CBT has been shown to be effective for the treatment of social anxiety in children and adults, but even after treatment, approximately 40% may remain diagnosable. Read more about this study
- Who is it for?
- Ages 8 to 55 years
- Conditions the study is for
- Phobic Disorders, Anxiety, Social Phobia
- What is being tested?
- D-Cycloserine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2005to Aug 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 8 to 55 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Subjects between 8 yrs of age (preadolescents) and under 55 yrs of age.
- Subjects medically healthy.
- Able to give informed consent.
- Not on psychotropic meds for a minimum of 6 weeks for fluoxetine; a minimum of 1 week for PRN benzodiazepines and beta blockers, and a minimum of 3 weeks for all other psychotropic meds.
- Subjects diagnosed with DSM IV symptoms of social phobia, generalized or specific type.
Who cannot join
- Current major depressive disorder.
- Lifetime diagnosis of psychotic disorder, bipolar disorder, eating disorder, mental retardation, substance or alcohol dependence (other than nicotine); active suicidal ideation.
- Current or lifetime history of a neurological disorder (other than tic disorders, febrile seizures of infancy), seizure disorder.
- Any unstable medical condition.
- Use of any psychoactive substance in the past 30 days.
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: Effect of D-Cycloserine on Treatment of Social Phobia
This study examines whether an antibiotic, d-cycloserine (DCS), boosts the effectiveness of cognitive behavior therapy (CBT) for social anxiety. CBT has been shown to be effective for the treatment of social anxiety in children and adults, but even after treatment, approximately 40% may remain diagnosable. The antibiotic DCS has been shown to enhance the type of learning that is promoted by exposure therapy, a main component of CBT. This study will test whether DCS can improve the effectiveness of CBT for social anxiety.
All participants will receive 12 weekly CBT sessions. In addition to receiving the CBT, participants will be randomly assigned (similar to a coin toss) to receive either DCS or a placebo (sugar pill). The pill will be taken 1-2 hours prior to each of the 12 CBT sessions. The pill is taken only on the 12 therapy days.
Read more
Prior to receiving treatment, participants will be asked to:
- participate in interviews to assess diagnosis and how they are doing including mood, degree of nervousness and behavior
- have a physical examination, a urine test, and an electrocardiogram (EKG)
- undergo tests involving problem-solving and memory
- prepare and present a speech to a "virtual audience" using virtual reality goggles
- undergo functional magnetic resonance imaging (fMRI) while performing tasks that involve looking at pictures, remembering things, testing reaction times, and making simple choices
Those who have not improved by the end of the study will be offered standard antianxiety medication treatment for 1 to 3 months. If a participant does not wish to take medication, study clinicians will help him/her locate psychological care in the community. Participants will be asked to complete a follow-up assessment 3 months after their last CBT session.
Read the detailed description
Social phobia afflicts between 3%-15% of the US population. As such, it is a particularly common debilitating psychiatric disorder. Like many anxiety disorders, social phobia typically arises during adolescence. Treatment has consisted of medication or cognitive behavioral therapy (CBT). Selective Serotonin Reuptake Inhibitors (SSRIs) represent the first-line pharmacological treatment both in adults as well as adolescents (APA Treatment Guidelines 2004). Similarly, CBT significantly improves outcome in both age groups. This treatment consists of psychoeducation, exposure therapy, and cognitive restructuring. While both treatments produce clinically meaningful benefits, most patients exhibiting positive responses to these treatments continue to exhibit marked residual symptoms, if not full-blown anxiety disorders. Thus, there is great need for treatment advances.
Intense fear of social scrutiny represents a core component of social phobia, and extinction of this fear represents the goal of exposure therapy during CBT (Cohn and Hope). Finding treatments that facilitate extinction is of paramount importance. In animals, extinction involves an active learning process that is blocked by glutamatergic NMDA antagonists and facilitated by NMDA agonists. Specifically, administration of D-cycloserine (DCS), a partial agonist at the glycine modulatory site on the NMDA receptor, produces a dose-dependent facilitation of extinction in the rat. As such, DCS might facilitate extinction during exposure-based CBT. Indeed, Ressler (Ressler et al 2004) recently reported preliminary data from a clinical trial supporting this hypothesis.
We will examine the degree to which DCS treatment can augment the clinical response in social phobia to CBT-exposure-based therapy. Specifically, we will study two groups of individuals with social phobia, both of whom will receive CBT. One group will receive placebo; a second group will receive 50 mg of D-cycloserine 1-2 hours before each exposure therapy session. We hypothesize that compared to placebo, DCS will produce greater reductions in social anxiety symptoms following CBT treatment. Finally, given that chronic social anxiety disorder virtually always begins during childhood, it is particularly vital to develop early interventions for the disorder. Accordingly, our trial will examine both adolescents and adults with the disorder.
- Conditions
- Phobic Disorders, Anxiety, Social Phobia
- Being tested
- D-Cycloserine, Placebo
- Keywords
- Cognitive, Behavioral, Adolescent, Therapy, Extinction, Social Phobia
- Medical subject headings
- Phobic Disorders, Anxiety Disorders, Phobia, Social, Behavior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
D-CycloserineDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| D-Cycloserine | Active comparator | An antibiotic, d-cycloserine (DCS) was given to one group and the group is evaluated to see if the drug boosts the effectiveness of cognitive behavior therapy (CBT) for social anxiety. Receives: Drug: D-Cycloserine |
| Placebo | Placebo comparator | Another group was given the placebo and tested for effectiveness of cognitive behavior therapy (CBT) for social anxiety. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Global Improvement (CGI-S) Scale
Symptom severity and improvement was assessed using the Clinical Global Impressions scale (CGI). It is a 2-item clinician-administered instrument that measures the patients' illness severity and global improvement. The minimum value for the CGI is 1=Normal, not at all ill and the maximum value is 7=Among the most extremely ill patients.
Measured: 12 weeks post baseline
Secondary outcomes (1)
Liebowitz Social Anxiety Scale (LSAS)
Social anxiety symptoms were assessed using the Liebowitz Social Anxiety Scale (LSAS). It is a 24-item self-report instrument that measures overall social anxiety fear and avoidance symptoms. This is the baseline assessment. The 24 items are each rated twice, from a "0" to "3" scale, with "0" indicated no level of symptom and "3" indicating a high level of the system. One rating is for anxiety, and the other is for avoidance. Thus, the lowest possible score is 0, and the highest possible score is 144. The total score represents the simple sum of all 48 ratings.
Measured: 12 weeks post baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2005 (estimated)
- Study startAug 2005
- Primary completionJun 2012
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Phobic DisordersStudies 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Jennifer A Cameron, C.R.N.P., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00128401
- Sponsor's protocol ID
- 050198
- Other IDs
- 05-M-0198
- Status last verified
- Apr 2014
- First submitted
- 8 Aug 2005
- Last updated
- 20 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Alstrom JE, Nordlund CL, Persson G, Harding M, Ljungqvist C. Effects of four treatment methods on social phobic patients not suitable for insight-oriented psychotherapy. Acta Psychiatr Scand. 1984 Aug;70(2):97-110. doi: 10.1111/j.1600-0447.1984.tb01187.x.
PubMed 6148843Butler G, Cullington A, Munby M, Amies P, Gelder M. Exposure and anxiety management in the treatment of social phobia. J Consult Clin Psychol. 1984 Aug;52(4):642-50. doi: 10.1037//0022-006x.52.4.642. No abstract available.
PubMed 6147366D'Souza DC, Gil R, Cassello K, Morrissey K, Abi-Saab D, White J, Sturwold R, Bennett A, Karper LP, Zuzarte E, Charney DS, Krystal JH. IV glycine and oral D-cycloserine effects on plasma and CSF amino acids in healthy humans. Biol Psychiatry. 2000 Mar 1;47(5):450-62. doi: 10.1016/s0006-3223(99)00133-x.
PubMed 10704956
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of D-Cycloserine on Treatment of Social Phobia
- ClinicalTrials.gov ID
- NCT00128401
- Acronym / sponsor ID
- 050198
- Conditions
- Phobic Disorders, Anxiety, Social Phobia
- Keywords
- Cognitive, Behavioral, Adolescent, Therapy, Extinction, Social Phobia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- Aug 2005
- Primary completion
- Jun 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 9 Aug 2005 (estimated)
- Results
- Posted 20 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study examines whether an antibiotic, d-cycloserine (DCS), boosts the effectiveness of cognitive behavior therapy (CBT) for social anxiety. CBT has been shown to be effective for the treatment of social anxiety in children and adults, but even after treatment, approximately 40% may remain diagnosable. The antibiotic DCS has been shown to enhance the type of learning that is promoted by exposure therapy, a main component of CBT. This study will test whether DCS can improve the effectiveness of CBT for social anxiety.
All participants will receive 12 weekly CBT sessions. In addition to receiving the CBT, participants will be randomly assigned (similar to a coin toss) to receive either DCS or a placebo (sugar pill). The pill will be taken 1-2 hours prior to each of the 12 CBT sessions. The pill is taken only on the 12 therapy days.
Prior to receiving treatment, participants will be asked to:
- participate in interviews to assess diagnosis and how they are doing including mood, degree of nervousness and behavior
- have a physical examination, a urine test, and an electrocardiogram (EKG)
- undergo tests involving problem-solving and memory
- prepare and present a speech to a "virtual audience" using virtual reality goggles
- undergo functional magnetic resonance imaging (fMRI) while performing tasks that involve looking at pictures, remembering things, testing reaction times, and making simple choices
Those who have not improved by the end of the study will be offered standard antianxiety medication treatment for 1 to 3 months. If a participant does not wish to take medication, study clinicians will help him/her locate psychological care in the community. Participants will be asked to complete a follow-up assessment 3 months after their last CBT session.
Detailed description
Social phobia afflicts between 3%-15% of the US population. As such, it is a particularly common debilitating psychiatric disorder. Like many anxiety disorders, social phobia typically arises during adolescence. Treatment has consisted of medication or cognitive behavioral therapy (CBT). Selective Serotonin Reuptake Inhibitors (SSRIs) represent the first-line pharmacological treatment both in adults as well as adolescents (APA Treatment Guidelines 2004). Similarly, CBT significantly improves outcome in both age groups. This treatment consists of psychoeducation, exposure therapy, and cognitive restructuring. While both treatments produce clinically meaningful benefits, most patients exhibiting positive responses to these treatments continue to exhibit marked residual symptoms, if not full-blown anxiety disorders. Thus, there is great need for treatment advances.
Intense fear of social scrutiny represents a core component of social phobia, and extinction of this fear represents the goal of exposure therapy during CBT (Cohn and Hope). Finding treatments that facilitate extinction is of paramount importance. In animals, extinction involves an active learning process that is blocked by glutamatergic NMDA antagonists and facilitated by NMDA agonists. Specifically, administration of D-cycloserine (DCS), a partial agonist at the glycine modulatory site on the NMDA receptor, produces a dose-dependent facilitation of extinction in the rat. As such, DCS might facilitate extinction during exposure-based CBT. Indeed, Ressler (Ressler et al 2004) recently reported preliminary data from a clinical trial supporting this hypothesis.
We will examine the degree to which DCS treatment can augment the clinical response in social phobia to CBT-exposure-based therapy. Specifically, we will study two groups of individuals with social phobia, both of whom will receive CBT. One group will receive placebo; a second group will receive 50 mg of D-cycloserine 1-2 hours before each exposure therapy session. We hypothesize that compared to placebo, DCS will produce greater reductions in social anxiety symptoms following CBT treatment. Finally, given that chronic social anxiety disorder virtually always begins during childhood, it is particularly vital to develop early interventions for the disorder. Accordingly, our trial will examine both adolescents and adults with the disorder.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| D-Cycloserine | Active comparator | Drug: D-CycloserineAn antibiotic, d-cycloserine (DCS) was given to one group and the group is evaluated to see if the drug boosts the effectiveness of cognitive behavior therapy (CBT) for social anxiety. |
| Placebo | Placebo comparator | Drug: PlaceboAnother group was given the placebo and tested for effectiveness of cognitive behavior therapy (CBT) for social anxiety. |
Who may qualify
- Ages
- 8 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
Key exclusion criteria (5 listed)
- Current major depressive disorder.
- Lifetime diagnosis of psychotic disorder, bipolar disorder, eating disorder, mental retardation, substance or alcohol dependence (other than nicotine); active suicidal ideation.
- Current or lifetime history of a neurological disorder (other than tic disorders, febrile seizures of infancy), seizure disorder.
- Any unstable medical condition.
- Use of any psychoactive substance in the past 30 days.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| D-Cycloserine | Drug | D-Cycloserine |
| Placebo | Drug | Placebo |
Primary outcome
Clinical Global Improvement (CGI-S) Scale
Time frame: 12 weeks post baseline
Symptom severity and improvement was assessed using the Clinical Global Impressions scale (CGI). It is a 2-item clinician-administered instrument that measures the patients' illness severity and global improvement. The minimum value for the CGI is 1=Normal, not at all ill and the maximum value is 7=Among the most extremely ill patients.
1 secondary outcome
Liebowitz Social Anxiety Scale (LSAS)
Time frame: 12 weeks post baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 6148843Alstrom JE, Nordlund CL, Persson G, Harding M, Ljungqvist C. Effects of four treatment methods on social phobic patients not suitable for insight-oriented psychotherapy. Acta Psychiatr Scand. 1984 Aug;70(2):97-110. doi: 10.1111/j.1600-0447.1984.tb01187.x.
- Background: PubMed 6147366Butler G, Cullington A, Munby M, Amies P, Gelder M. Exposure and anxiety management in the treatment of social phobia. J Consult Clin Psychol. 1984 Aug;52(4):642-50. doi: 10.1037//0022-006x.52.4.642. No abstract available.
- Background: PubMed 10704956D'Souza DC, Gil R, Cassello K, Morrissey K, Abi-Saab D, White J, Sturwold R, Bennett A, Karper LP, Zuzarte E, Charney DS, Krystal JH. IV glycine and oral D-cycloserine effects on plasma and CSF amino acids in healthy humans. Biol Psychiatry. 2000 Mar 1;47(5):450-62. doi: 10.1016/s0006-3223(99)00133-x.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
Jennifer A Cameron, C.R.N.P. principal investigator
National Institute of Mental Health (NIMH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing D-Cycloserine in people with Phobic Disorders and Anxiety, 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 5 inclusion and 5 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 20 May 2014. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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.
What does the primary outcome measure?
Clinical Global Improvement (CGI-S) Scale (time frame: 12 weeks post baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00128401, which also lists 3 linked publications.
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 20 May 2014.