Clinical Trials Register

Summary
EudraCT Number:	2011-004177-83
Sponsor's Protocol Code Number:	37202
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2011-09-07
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

Netherlands - Competent Authority

A.2

EudraCT number

2011-004177-83

A.3

Full title of the trial

Boosting the oxytocin system in acute trauma: The effectiveness of intranasal oxytocin treatments and stimulation of social support on preventing trauma related psychopathology

Versterken van het oxytocine systeem in acuut trauma: de effectiviteit van oxytocine behandelingen en het stimuleren van sociale steun voor de preventie van traumagerelateerde psychopathologie

A.3.1

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

Oxytocine en social support after a traumatic event

Oxytocine en sociale steun na een ingrijpende gebeurtenis

A.3.2

Name or abbreviated title of the trial where available

Oxytocin and social support as early interventions in acute trauma

Oxytocine en sociale steun als vroege interventies na acuut trauma

A.4.1

Sponsor's protocol code number

37202

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	Academic Medical Center
B.1.3.4	Country	Netherlands
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	Academic Medical Center, Research Counsil
B.4.2	Country	Netherlands
B.4.1	Name of organisation providing support	ZonMw
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Academic Medical Center, Department of Psychiatry, Center for Anxiety Disorders
B.5.2	Functional name of contact point	Olff Oxytocine-Research Group
B.5.3	Address:
B.5.3.1	Street Address	Meibergdreef 5
B.5.3.2	Town/ city	Amsterdam
B.5.3.3	Post code	1105 AZ
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31(0)208913662
B.5.5	Fax number	+31(0)208913664
B.5.6	E-mail	m.olff@amc.uva.nl

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
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	Syntocinon, nasal spray 40 IU/ml
D.2.1.1.2	Name of the Marketing Authorisation holder	Defiante Farmacêutica, SA
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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.3.4	Pharmaceutical form	Nasal spray, solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intranasal use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	50-56-6
D.3.9.3	Other descriptive name	OXYTOCIN
D.3.9.4	EV Substance Code	SUB09580MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40
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
D.8.3	Pharmaceutical form of the placebo	Nasal spray, solution
D.8.4	Route of administration of the placebo	Intranasal use (Noncurrent)

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Posttraumatic Stress Disorder (PTSD) according to criteria in the DSM-IV

Posttraumatische Stress Stoornis (PTSS) volgens de DSM-IV

E.1.1.1

Medical condition in easily understood language

posttraumatic stress disorder

posttraumatische stress stoornis

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	14.0
E.1.2	Level	PT
E.1.2	Classification code	10036316
E.1.2	Term	Post-traumatic stress disorder
E.1.2	System Organ Class	10037175 - Psychiatric disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

In recently traumatized individuals (at the latest on day ten post trauma exposure) with a high initial level of distress, we aim to assess the effectiveness of intranasal OT and a semi-structured social support intervention in preventing symptoms of PTSD at one and three months post trauma follow-up.

Het primaire studiedoel is om in recent getraumatiseerden met een hoog niveau van acute stress-klachten de effectiviteit van intranasale oxytocine (OT) behandelingen en een semi-gestructureerde sociale steun interventie op PTSS symptomen tijdens één en drie maanden na het trauma te onderzoeken.

E.2.2

Secondary objectives of the trial

• Investigate the effects of oxytocine (OT) and social support intervention on depression and general anxiety symptoms, psychophysiological and neuroendocrine measures, perceived social support and psychological functioning after one week, and at one, three and six months post trauma follow-up;
• Examine potential associations between the main study outcome and gender, genetic variation, subjective measures of social support, representations of attachment style, coping style, subjective health complaints, affect, quality of life, trauma type and history of (childhood) trauma and life events.

- het onderzoeken van het effect van de OT en de sociale steun interventie op depressie en algemene angst symptomen, psychofysiologische / neuroendocriene maten, de ervaren sociale steun en psychologisch functioneren op één week na de eerste behandeling en op één, drie en zes maanden na traumablootstelling.
- het onderzoeken van de potentiële associaties tussen de primaire studie-uitkomst en geslacht, genetische variatie, ervaren sociale steun, hechtingsstijl, coping stijl, subjectieve gezondheidsklachten, affect, kwaliteit van leven, trauma type en eerder trauma (in de kindertijd).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

● Presentation at the Trauma Unit or Emergency Department after a potential traumatic event, according to PTSD A1 criterion in the DSM-IV
● Trauma Screening Questionnaire (TSQ) > 5 between 24 and 72 hours after trauma exposure
● Age 18 – 65 years
● Significant other (i.e. best friend, partner or family member) willing to join the social support intervention
● Capable to read and comprehend either the Dutch or English language

● Presentatie op de Trauma Unit of Spoedeisende Hulp na een potentiëel traumatische gebeurtenis volgens PTSD criterium A1 in de DSM-IV
● Trauma Screening Questionnaire (TSQ) > 5, tussen 24 en 72 uur na blootstelling aan trauma
● Leeftijd 18 – 65 jaar
● Significante ander (i.e. beste vriend(in), partner of familielid) die bereid is om deel te nemen aan de sociale steun interventie
● Schriftelijke toestemmingsverklaring
● Het voldoende beheersen van de Nederlandse taal om het te lezen en te begrijpen

E.4

Principal exclusion criteria

● Any severe or chronic systemic disease
● Current psychotic, bipolar, substance-related, severe personality disorder, or mental retardation
● Current severe depressive disorder
● Prominent current suicidal risk or homicidal ideation
● Severe cognitive impairment or a history of organic mental disorder
● Evidence of PTSD or depression immediately prior to the index trauma
● History of neurological disorders (e.g., traumatic brain injury, seizure history)
● Reports of ongoing traumatization (e.g., in case of partner violence as index adult trauma)
● Evidence of clinically significant and unstable medical conditions in which OT administration is contra-indicative such as cardiovascular, gastro-intestinal, pulmonary, severe renal, endocrine or hematological disorders, glaucoma, history of epilepsy, or a stroke or myocardial infarction within the past year
● Use of prostaglandins and certain anti-migraine medications (ergot alkaloids)
● Sensitivity or allergy for OT or its components (e.g., methylhydroxybenzoate and propylhydroxybenzoate)
● Impaired consciousness, or amnesia or confusion (due to for example head injury) (Glasgow Coma Scale lower than 13)
● Female participants: pregnancy and breast feeding (NB. Female participants with childbearing potential must have a negative pregnancy test).

- Een ernstige of chronische systemische ziekte
- huidige psychotische, bipolaire, middelengerelateerde, ernstige persoonlijkheidsstoornis, of mentale retardatie
- huidige ernstige depressieve stoornis
- Huidig suïcide risico of suïcidale ideatie
- Ernstige cognitieve beperking of een organische mentale stoornis in de anamnese
- Aanwijzingen voor PTSS of depressie vlak voor het index trauma
- Neurologische stoornis in de anamnese (bv. traumatisch hersenletsel, convulsies)
- Aanwijzingen voor continuerende traumatisatie (bv in het geval van partner geweld als index trauma)
- Aanwijzingen voor klinisch significante,onstabiele medische toestand, waarbij een contraindicatie bestaat voor toediening van oxytocine, zoals cardiovasculaire, gastro-intestinale, pulmonaire, renale, endocriene of hematologische stoornissen, glaucoom, epilepsie in de anamnese, of een beroerte of myocardinfarct in het afgelopen jaar.
- Het gebruik van prostaglandines en bepaalde anti-migraine medicatie (ergot alkaloides)
- Overgevoeligheid/allergie voor oxytocine of de bestanddelen (bv methylhydroxybenzoaat en propylhydroxybenzoaat)
- Aangetast bewustzijn, of amnesie of verwarring (ten gevolg van bijvoorbeeld hoofd letsel) (Glasgow Coma Scale < 13)
- Vrouwelijke proefpersonen: zwangerschap, borstvoeding (NB. vrouwelijk proefpersonen in de vruchtbare leeftijd moeten een negatieve zwangerschapstest hebben)

E.5 End points

E.5.1

Primary end point(s)

The main study outcome is the difference in PTSD symptoms severity (CAPS scores) between the four trial arms (i.e. oxytocine (OT) + social support; placebo + social support; OT + no intervention additive to care as usual; placebo + no intervention additive to care as usual) at one and three months post trauma follow-up.

De primaire studie-uitkomst is het verschil in ernst van PTSS symptomen (CAPS score) tijdens 1 en 3 maanden na trauma follow-up tussen de vier studie-armen (oxytocine (OT) + sociale steun; OT + geen toegevoegde sociale steun interventie; placebo + sociale steun; placebo + geen toegevoegde sociale steun interventie).

E.5.1.1

Timepoint(s) of evaluation of this end point

1 and 3 months post trauma

1 en 3 maanden na trauma

E.5.2

Secondary end point(s)

• Difference between the four groups in depression and general anxiety symptoms, neuroendocrine and psychophysiological measures, perceived social support and psychological functioning after one week of OT treatments, and one, three and six months post trauma exposure.
• Potential associations between the main study outcome and gender, genetic variation, subjective measures of social support, representations of attachment style, coping style, subjective health complaints, affect, quality of life, trauma type, history of (childhood) trauma and life events.

- Verschillen tussen de vier groepen in depressieve en algemene klachten, psychofysiologische en neuroendocriene parameters, subjectieve sociale steun en psychologisch functioneren één week na de eerste behandeling en tijdens één, drie, en zes maanden na trauma follow-up.
- Associaties tussen de primaire studie uitkomstmaten en geslacht, genetische variatie, subjectieve maten van sociale steun, hechtingsstijl, coping stijl, subjectieve gezondheidsklachten, affect, kwaliteit van leven, trauma type en verleden van trauma (in de kindertijd).

E.5.2.1

Timepoint(s) of evaluation of this end point

7-10 days after trauma; 14-17 days after trauma; 1, 3, 6 months after trauma

7-10 dagen na trauma; 14-17 dagen na trauma; 1, 3 en 6 maanden na trauma

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

Yes

E.6.4

Safety

E.6.5

Efficacy

Yes

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

E.6.13

Others

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

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

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Psychosociale steun interventie

Psychosocial support intervention

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the 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

When all included participants finished all assessments or have dropped out

Wanneer alle geincludeerde patienten alle metingen hebben afgerond of niet meer deelnemen aan de studie

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

260

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2011-09-07.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

Yes

F.3.3.7.1

Details of other specific vulnerable populations

Recently traumatized individuals

Recent getraumatiseerde personen

F.4 Planned number of subjects to be included

F.4.1

In the member state

260

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

care as usual, if necessary

care as usual, indien nodig

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2011-09-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-11-14

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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