The first objective of this study is whether DCS addition to exposure therapy enhances symptom reduction in PD+AGO. The second objective of the study is to establish the optimal timing of administration of D-cycloserine (directly pre- or post…
ID
Source
Brief title
Condition
- Anxiety disorders and symptoms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome measures will be:
- the Panic Disorder Severity Scale (PDSS; Shear et al. 1997; taken weekly
before each session)
- the Subjective Unit of Distress Scale (SUDS; Wolpe 1969), taken weekly before
and after each session.
Secondary outcome
Secondary outcome measures:
The following measures will be taken at baseline, after the 4th and 7th
sessions, post-test and FU:
- Beck Anxiety Inventory (BAI; Beck, 1990)
- the Agoraphobic Cognitions Questionnaire (ACQ, Chambless, 1985).
- the Mobility Inventory (MI; Chambless, 1985; measures amount of agoraphobic
avoidance; taken after every three sessions).
- Beck depression inventory II (BDI-II, Beck, 1987) of Hamilton (Alleen bij
baseline of doen we alleen BDI?)
- Outcome Questionnaire (OQ-45; Lambert, Huefner, & Reisinger, 1996)
- Sheehan Disability Scales (SDS; Sheehan, 1998).
- WHOQOL (Quality of Life; WHOQOL Group, 1996)
- The Body Symptoms Questionnaire (BSQ; Chambless,1985)
- Positive and Negative Affect Shedule (Watson, Clark & Tellegen, 1988)
- The Fawcett side effects checklist (Fawcett, 1987).
Neuropsychological tests:
To investigate how DCS affects memory, learning and executive tasks, the
following neuropsychological tests are administered at baseline, post-treatment
and FU
Intelligence: Nederlandse Leestest voor Volwassenen (NLV; Schmand, Lindeboom &
van Harskamp, 1992). This is a 5-minute lasting reading task in which persons
have to read aloud words with varying difficulty and frequency of mistakes and
speed are monitored as outcome variables. This task is well validated in the
Netherlands.
Contextual learning. This task will be administered at baseline, at the UU. A
virtual environment is setted at the UU (Baas et al, 2008). The participants
will get a shock(US, individually only in a specific context, combined with a
specific stimulus (shock). Time to learn this context will be measured.
Another part of this test is the auditory startle-fase, in which the height of
the physical reaction on a stimulus is measured. We used a validated procedure
by J. Baas, earlier approved by the METC (procotol 05-166).The investigators
have used shocks in various experiments in over 600 subjects in the last 4
years at NIMH, and in about 200 subjects at Utrecht University. The shock is
generally described by subjects as rather anxiogenic and unpleasant, but not
painful. The mean rating of aversiveness on a scale of 1 (not at all painful)
to 10 (extremely painful) is about 5. Approximately 80% of the subjects rate
the shock between 4 and 6, 10% below 4, and 10% above 6. The effects of these
shocks are similar to that of snapping a tight rubber band against the skin.
Subjects will have the opportunity to withdraw from the study if they wish at
any moment, and are informed explicitly about this option in the informed
consent. Our experience is that after an experiment involving shocks over 95%
of subjects indicated to have no problem returning for a follow-up experiment.
Extinction task:
This task will be administated at the location of the therapy, before session
4. To determine how DCS facilitates the process of extinction, a version of the
experimental task, descibed by Engelhard et al (2009) will be used. We assume
that participants are already conditioned for agoraphobic stimuli. After
offering an unconditioned stimulus (using head phones, participants will hear a
white noise, 500 ms, 95 dB) agoraphobic and neutral words will be offered
(using a notebook). These words will NOT be followed by the noise and
participants are asked to fill in their expectancy of hearing a tone following
a word (using VAS scales). Half way the experiment the tone will be repeated to
reinstate expectancy. The decrease of the expectancy will be measured
(extinction) and our hypothesis is that DCS facilitates this extinction. This
task will be administered before session 4, when part of the participants has
received DCS. The loudness of the tone is tested by Engelhard et al (2009) and
has been proved to be well tolerated.
Cost effectiveness measurement:
- Care use and work loss are measured at baseline, post- test and FU, by the
Trimbos/iMTA questionnaire for Costs associated with: Psychiatric Illness
(TiC-P; Hakkaart-van Roijen, 2002).
Finally, at baseline buccal swabs will be taken for genetic material, after
separate informed consent has been obtained from the study subjects.
Background summary
Panic Disorder + agoraphobia (PD + AGO) is an anxiety disorders that are among
the most prevalent disorders in mental health care. Currently, behavior therapy
(exposure therapy) is the treatment of choice, either alone or in combination
with serotonin reuptake inhibitors. Although exposure therapy has proven to
result in significant symptom reduction in about 60% of patient, a significant
number of individuals fail to respond to sufficiently treatment.
Procedurally, exposure therapy is based on extinction of condicitioned fear.
Recent work in rodents and humans has demonstrated that acute treatment with
D-cycloserine (DCS) a partial agonist of the NMDA-receptor, enhances the
learning and memory processes underlying extinction of fear. It is of great
interest to study wheter addition of DCS to exposure therapy in patients with
anxiety disorders leads to improvement of treatment effect, speed of exposure
therapy effect and/ or, as a consequence, diminished costs. In OCD, the first
clinical studies performed so-far strongly suggest that DCS, administered
either within 1 hour before or directly after exposure therapy , enhances the
effect of the therapy in the first 5-6 sessions. In pannic disorder -the
"model" anxiety disorder-, DCS has barely been investigated, but the first
results of enhancement with DCS of interceptive exposure to panic sensations
suggest enhanced treatment effect and higher remission rates in patients. This
study aims at extending current knowledge about exposure therapy enhancing
effects of DCS in PD + AGO.
Study objective
The first objective of this study is whether DCS addition to exposure therapy
enhances symptom reduction in PD+AGO. The second objective of the study is to
establish the optimal timing of administration of D-cycloserine (directly pre-
or post exposure therapy). The third objective is, to study the fear extinction
enhancenment of DCS using a neuropsychological paradigm. The fourth objective
is, from a health economic perspective, to esthablish cost-effectiveness of
DCS. The hypotheses are that improvement will occur, at a faster rate, with
addition of DCS, which will result in less therapy sessions needed and thus
cost reduction. Are there specific genotype profiles related to a) favourable
response to exposure therapy and b) enhanced effect of DCS?
Study design
This double blind placebo controled trial involves 60 patients with PD+AGO,
randomized treatment with either placebo, or single fixed dosages of 125 mg DCS
in the first 6 sessions of a 12 session program of exposure therapy, either 30
minutes before or after each weekly 60-90 minute standardized exposure therapy
session. Thus, patients with PD+AGO will be randomly allocated to 1 of 3
possible conditions. Patients in condition 1 will receive DCS before and
placebo after exposure sessions. Patients in condition 2 will receive Placebo
both before and after exposure sessions. Patients in condition 3 will receive
placebo before and DCS after exposure sessions. This study is a colleborative
project between the department of Psychiatry, AMC on the one hand, and the
Academic Anxiety outpatient clinic of Altrecht Utrecht and the Department of
clinical psychology, Utrecht University (Dr. Cath, principal Investigator) on
the other. For patient recruitment and inclusion, departments will collaborate
with the anxiety outopatient clinic GGZ InGeest Amsterdam and the anxiety
outpatient clinic of Meerkanten, Ermelo.
Treatment effect and effects on fear extinction, learning and habituation are
measured after each session, directly post treatment (after 12 exposure
sessions) and at 6 months follow-up. Health care use and costs, quality of
life, and loss of work productivity are measured pre, directly post treatment
and at follow-up.
Intervention
Exposure therapy, by protocol, and depending on the condition a possible
medical intervention by D-cycloserine.
Study burden and risks
This study can make a contribution to a better understanding of how and what
kind of treatment is the best use of panic disorder with agoraphobia.
It is expected that this research does not bring any harm to the patient,
partly because the DCS dose many times lower than the standard dose for
treatment of Tubercolosis. Research shows that there are minimal side effects
at this dose, however, most patients do not note any.
The only burden is that the patient will be requested to invest some sime for
extra measurements.
A burden for the subjects is that they have to invest some time in interviews
with the investigators, completing questionnaires and neuropsychological tests.
Heidelberglaan 1
3584 CB UTRECHT
Nederland
Heidelberglaan 1
3584 CB UTRECHT
Nederland
Listed location countries
Age
Inclusion criteria
Adults patients (between 18 and 55 years) with panic disorder + agoraphobia (PD+AGO), according to DSM-IV diagnoses as established using standardized interviews. And are referred to the outpatient clinic of one of the participating centres.
Exclusion criteria
Patients with :
- co-morbided psychiatric disorders (severe major depressive disorder, bipolar disorder, psychosis, dependence and abuse of alcohol, drugs in the past three months)
- mental deficiency
- inability to adequately read or speak Dutch
- (a history of) neurological disease (i.e. neurovascular disease, movement disorders, seizures, dementia), renal or liver abnormalities, and a history of allergies, adverse reactions or rash on medication.
- Currently taking benzodiazepines, since benzodiazepine might hamper therapy effect.
- Pregnancy or breastfeeding at the time of the study
- use of isoniazide and cycloserines.
- use of variable dosages of antidepressiva (SSRI*s of TCA)( the use of a fixed dosage of antidepressiva is NOT an exclusion criterium)
- An evidence based behavioural therapy for panic disorder during the past 12 month.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | 2050 |
| EudraCT | EUCTR2009-012918-51-NL |
| CCMO | NL29755.041.09 |