Clinical Trials Register

Summary
EudraCT Number:	2013-003219-22
Sponsor's Protocol Code Number:	LMS/SF/UH/0018
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-12-02
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2013-003219-22

A.3

Full title of the trial

A randomised controlled feasibility trial comparing clinical and cost effectiveness of cognitive behavioural therapy (CBT) and selective serotonin reuptake inhibitors (SSRI) and their combination in the management of obsessive compulsive disorder.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Optimal Treatment for Obsessive Compulsive Disorder Trial

A.3.2

Name or abbreviated title of the trial where available

Optimal Treatment for OCD (OTO) Version 1.0

A.4.1

Sponsor's protocol code number

LMS/SF/UH/0018

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Hertfordshire Partnership University NHS Foundation Trust
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	National Institute of Health Research
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University of Hertfordshire
B.5.2	Functional name of contact point	Solange Wyatt
B.5.3	Address:
B.5.3.1	Street Address	University of Herts, College Lane
B.5.3.2	Town/ city	Hatfield
B.5.3.3	Post code	Al10 9AB
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	01707284642
B.5.5	Fax number	01707285104
B.5.6	E-mail	s.wyatt5@herts.ac.uk
B.Sponsor: 2
B.1.1	Name of Sponsor	University of Hertfordshire
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Hertfordshire Partnership University Foundation NHS Trust
B.4.2	Country	United Kingdom
B.4.1	Name of organisation providing support	South West London and St Georges Mental Health NHS Trust
B.4.2	Country	United Kingdom
B.4.1	Name of organisation providing support	Southern Health NHS Foundation Trust
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University of Hertfordshire
B.5.2	Functional name of contact point	Solange Wyatt
B.5.3	Address:
B.5.3.1	Street Address	Health Research Building, College Lane Campus
B.5.3.2	Town/ city	Hatfield
B.5.3.3	Post code	AL10 9AB
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	01707284642
B.5.5	Fax number	01707285104
B.5.6	E-mail	s.wyatt5@herts.ac.uk

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Sertraline
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Sertraline
D.3.2	Product code	Generic sertraline
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Sertraline
D.3.9.1	CAS number	79559-97-0
D.3.9.2	Current sponsor code	LMS/SF/UH/00018
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	50 to 200
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Obsessive Compulsive Disorder

E.1.1.2

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10037174
E.1.2	Term	Psychiatric disorder NOS
E.1.2	System Organ Class	100000004873

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The main research question is to find out whether it is possible to carry out a randomised study looking at whether sertraline alone or cognitive behavioural therapy alone or a combination of both sertraline and cognitive behavioural therapy is better in treating obsessive compulsive disorder (OCD). The study will look at what obstacles there are in recruiting into a large trial, the practicality of delivering treatment and the acceptability to patients. Symptom changes, quality of life changes and resource use will also be assessed.

E.2.2

Secondary objectives of the trial

Outcome measures will be evaluated. The variation in the Y-BOCS (a specific questionnaire looking at obsessions and compulsions to assess OCD severity) both within and between the three treatment arms will be evaluated. The following outcomes will also be evaluated to assess the influence on patient selection and on the change in Y-BOCS score. This will help inform the need for adjusted and stratified analysis within the large trial. The endpoints will be evaluated to enable appropriate estimation of sample size required for a full-scale trial.
-Clinical Global Impression (CGI) Symptom Scale and CGI Improvement Scale (a scale to assess the clinical state of the patient)
-Sheehan Disability Scale (a scale to look at how symptoms affect your life)
-The Autistic Quotient (a questionnaire looking at autistic traits)
-The Montgomery Asberg Depression Rating Scale
-CANTAB: Stop signal reaction time; ID-ED; Affective go-no-go; Cambridge gamble task (computerised tasks to look at cogn

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) Community based service-users, aged 18-65 years.
2) DSM-IV OCD, determined by a psychiatrist using the MINI for DSM-IV
3) Duration of symptoms >1 year (from medical history)
4) Baseline score >16 on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS)

E.4

Principal exclusion criteria

1) History of psychotic disorder (schizophrenia, psychotic symptoms, bipolar disorder), Tourette syndrome(tic disorders not amounting to Tourette syndrome will not be exclusionary), organic mental disorder, psychosurgery, personality disorder of borderline or histrionic type.
2) Alcohol/substance-abuse disorders within the past 12 months.
3) Any other DSM-IV Axis I disorder that is considered the primary focus of treatment
4) Severe depression, defined by a Montgomery-Asberg Depression Rating Scale (MADRS) >30 at baseline.
5) Actively planning suicide (scoring >4 on item 10 of MADRS)or judged by the clinician to be at significant risk of self-harm.
6) Attended CBT involving ERP from an accredited (British Association of Behavioural and Cognitive Psychotherapies (BABCP) approved or equivalent) therapist (eg. IAPTs stage 2) in the last 6 months.
7) Failed (inadequate clinical response, equivalent to <25% improvement) >=2 previous adequate (>12weeks) trials of CBT involving ERP from an accredited (BABCP-approved or equivalent) therapist.
8)Failed (inadequate clinical response,equivalent to <25% improvement) >=2 previous adequate (>12weeks) trials of any SSRI or clomipramine taken at optimal doses (if maximum SPC dose, evidence of intolerance of the higher dose is needed) with adequate adherence.
9) Needing regular psychotropic drugs other than study medication during the study (except hypnotics which will be allowed provided the dose has been stable for >12 weeks and remains so throughout the study period).
10) Currently involved in a treatment research study.
11)Acute or unstable physical illness including Hepatitis, HIV/AIDS, Creutzfeldt-Jakob disease
12) Needing regular specified medication known to interact adversely with sertraline.
13)Individual reasons making it difficult to comply with the treatment-programme, including the wash-out period.
14)Inadequate understanding of English to participate in treatment or give informed consent.
15) Women of child-bearing age not using reliable contraception.
16) Pregnant or breast-feeding women.
17) History of liver disease.
18) Epilepsy.
19) History of cardiovascular disease or blood disorders that increase bleeding tendency. eg. platelet disorder.

E.5 End points

E.5.1

Primary end point(s)

The primary outcome for the study is to assess the feasibility to inform a larger clinical trial. This will be done by evaluating the number of patients willing to be randomised, evaluating the differences in methods of identifying patients, investigating premature discontinuation rates, evaluating tolerability across treatment arms and assessing resource use and quality of life. Outcome measures will also be evaluated to estimate the sample size required for a large trial. For the outcome measures the primary endpoint is to estimate the variation in the Y-BOCS both within and between the three treatment arms.

E.5.1.1

Timepoint(s) of evaluation of this end point

The Y-BOCS will be completed at screening, baseline, week 2, week 4, week 8, week 16, week 32 and week 52.

The trial management group will evaluate the progress (patient recruitment, discontinuation rates, tolerability) of the trial on an ongoing basis.

E.5.2

Secondary end point(s)

The following outcome measures will be evaluated to assess the influence on patient selection and on the change in Y-BOCS score which will help inform the need for adjusted and stratified analysis within the large trial.
-Clinical Global Impression (CGI) Symptom Scale and CGI Improvement Scale
-Sheehan Disability Scale
-The Autistic Quotient
-The Montgomery Asberg Depression Rating Scale
-CANTAB: Stop signal reaction time; ID-ED; Affective go-no-go; Cambridge gamble task
-CSRI
-EQ-5D

E.5.2.1

Timepoint(s) of evaluation of this end point

The SDS and MADRS will be evaluated at baseline, week 2, week 4, week 8, week 16, week 32 and week 52.
The CGI symptom scale and AQ will be evaluated only a baseline.
The EQ-5D, CSRI and CANTAB will be evaluated at baseline, week 16 and 52.
The CGI improvement scale will be evaluated at weeks 2,4, 8, 16, 32 and 52.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

Yes

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Feasibility

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Rater-blinded, 3-arm trial. Sertraline vs CBT vs combination of Sertraline + CBT

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Cognitive Behavioural Therapy

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of trial will be when the last patient has completed treatment and has been assessed for the 52 week visit and all questionnaires have been completed.ie.LPLV

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1