The primary objective of the study is to evaluate the efficacy of agomelatine (25-50 mg/day) compared to placebo on the reduction of Obsessive and Compulsive symptoms by using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) after 16 weeks of…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
psychiatrische en obsessieve en compulsieve stoornissen
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Y-BOCS total score (expressed as the change from baseline to last post-baseline
value on W0-W16 period) will be used to demonstrate the superiority of
agomelatine compared to placebo on OC symptoms.
Secondary outcome
- National Institute of Mental Health-Obsessive-Compulsive Scale score (NIMH-OC)
- CGI Severity of Illness and Global Improvement scores
- Obsessive Compulsive Visual Aanalogue Scale (OC-VAS)
- Montgomery and Asberg depression rating scale (MADRS) total score
- Hamilton Rating Scale for Anxiety (HAM-A) total score
- Getting off to sleep score, Quality of sleep score, Sleep awakening score and
Integrity of behaviour score obtained from the Leeds Sleep Evaluation
Questionnaire (LSEQ).
- Work, Social life and Family life scores obtained from Sheehan disability
scale
- Adverse events
- Sitting blood pressure (SBP (mmHg) and DBP (mmHg)) and heart rate (bpm).
- Body weight (kg) and BMI (kg/m²).
- Laboratory parameters.
Background summary
Obsessive-compulsive disorder (OCD) is a severe, chronic and disabling disorder
that affects 2 to 4% of the population.
Serotonin reuptake inhibitors (SRIs ) are the first line pharmacotherapy for
OCD and the only drugs approved by Health Authorities for the treatment of OCD.
Approximately 40% to 60% of the OCD patients are improved by a pharmacotherapy
with SRI.
The response to these products is only partial with a reduction of 20% to 40%
on the Y-BOCS.
The new antidepressant agomelatione has a distinct neurochemical profile. It is
a melatoninergic agonist and 5HT2C antagonist. The mechanism of action does not
imply 5-HT reuptake inhibition but some properties of agomelatine support its
potential interest as an alternative in the treatment of OCD patients.
Pre-clinical and clinical data have shown the involvement of 5-HT2C receptors
in the pathophysiology of OCD. Also circadian rhythms and sleep are frequently
altered in those patients . Agomelatine directly resets the electrical activity
of the suprachiasmatic nucleus and thus resynchronises experimentally disrupted
circadian rhythms. Besides its antidepressant activity, agomelatine showed an
early improvement of sleep disorders in depressed patients.
Study objective
The primary objective of the study is to evaluate the efficacy of agomelatine
(25-50 mg/day) compared to placebo on the reduction of Obsessive and
Compulsive symptoms by using the Yale-Brown Obsessive Compulsive Scale
(Y-BOCS) after 16 weeks of treatment in patients fulfilling DSM-IV-TR criteria
for OCD .
Study design
A 16 week randomized , double blind placebo-controlled international phase II
study with parallel arms. The dose of agomelatine is flexible (25mg/day with
possible increase to 50 mg/day after 8 weeks of treatment). 80 patients will be
included in the study (40 patients per arm). The expected duration of the
study for a patient is maximum 17 weeks + 10 days.
The study will be divided into the following periods:
- A run-in period without treatment (maximum 10 days between Selection and
Inclusion visits).
- A double-blind treatment period of 16 weeks (from W0 to W16).
- A follow-up period of 1 week without treatment after the end of the
double-blind period or in case of premature withdrawal.
Intervention
4 bloodsamples will be taken during the study for haematology and biochemistry
(at selection, W8,W12,W16). The total amount will not exceed 60ml. An ECG
needs to be performed during selection or inclusion visit. anyway the results
need to be available for inclusion.
Saliva samples need to be taken for pharmacokinetics at W8 and W12, 1, 2 and 3
hours after intake of the study drug.
Study burden and risks
cfr E2 and E9
Internationalelaan 57
B-1070 Brussel
BE
Internationalelaan 57
B-1070 Brussel
BE
Listed location countries
Age
Inclusion criteria
- Out patients, male or female, between 18 and 65 years inclusive with a primary diagnosis of Obsessive Compulsive Disorder (OCD) according to DSM-IV-TR. The diagnosis will be documented by the brief structured interview M.I.N.I.
- Patients previously treated for OCD with a first line pharmacological treatment, i.e, SRI with or without cognitive behavioural therapy .
- Y-BOCS total score * 20 (moderately to severely ill),
- Duration of OCD symptoms of at least one year,
- Requiring a treatment.
Exclusion criteria
cfr p. 25-26
- Episodic OCD, Exclusive hoarders, Early onset OCD
- Refractory patients defined as having not responded to 2 or more adequate treatments (medium or high) dose of a SRI for at least 12 weeks.
- Patients in psychiatric care for more than 5 years for OCD
- Naïve Patients (never received pharmacological treatment for OCD)
- Motor or verbal tic disorder (including Tourette*s),
- Substance or alcohol dependence or abuse
- personality disorders
- Severe or uncontrolled organic diseases, likely to interfere with the conduct of the study (e.g., neurologic, neoplasic, cardiovascular, pulmonary, digestive or metabolic disorders like unstabilized diabetes of type I or II, morbid obesity, untreated or uncontrolled arterial hypertension*),
- Any clinically relevant abnormality detected during the physical examination, ECG or laboratory tests likely to interfere with the study conduct or evaluation,
- Hepatic impairment (i.e. cirrhosis or active liver disease),
- ASAT or ALAT values * 2 times the upper reference value
- Total bilirubin * 2 times the upper reference value or ALAT and total bilirubin >ULN
- Alkaline Phosphatase * 3 times the upper reference value,
- Women of childbearing potential without effective contraception (oral contraceptive pill, Intra-uterine contraceptive device or condom) as well as
- pregnant or breastfeeding women
- Concomitant psychotropic medications are forbidden during the study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-016713-20-NL |
| CCMO | NL31624.018.10 |