Clinical Trials Register

Summary
EudraCT Number:	2022-000043-74
Sponsor's Protocol Code Number:	PNAS0122
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-05-05
Trial 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

Austria - BASG

A.2

EudraCT number

2022-000043-74

A.3

Full title of the trial

Defining and predicting neonatal inadaptation after gestational exposure to antidepressants: longitudinal exploratory analysis of psychoneuroendocrine risk factors and complications

A.3.1

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

Effects of depression and antidepressants on infants´ adaption after birth

A.3.2

Name or abbreviated title of the trial where available

Neonatal adaptation syndrome after antidepressant treatment

A.4.1

Sponsor's protocol code number

PNAS0122

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	Medical University of Vienna
B.1.3.4	Country	Austria
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	Medical University of Vienna
B.4.2	Country	Austria
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Medical University of Vienna
B.5.2	Functional name of contact point	PI, Alexander Kautzky
B.5.3	Address:
B.5.3.1	Street Address	Währinger Gürtel 18-20
B.5.3.2	Town/ city	Vienna
B.5.3.3	Post code	1090
B.5.3.4	Country	Austria
B.5.6	E-mail	alexander.kautzky@meduniwien.ac.at

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.2.1.1.2	Name of the Marketing Authorisation holder	unspecified
D.2.1.2	Country which granted the Marketing Authorisation	Austria
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	Antidepressants (SSRI, SNRI)
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.3.11 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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

major depressive disorder
poor neonatal adaptation syndrome (after antidepressant use during pregnancy)

E.1.1.1

Medical condition in easily understood language

depression
adaptation problems in infants due to antidepressants used by their mothers during pregnancy

E.1.1.2

Therapeutic area

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

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Major depression brings along disability and lifelong disease burden and is especially prevalent in women, who are commonly affected by MDD during pregnancy and require specialized care for harmonizing maternal and fetal needs. Gold-standard treatment with serotonin reuptake inhibitors (SRI) may cause an imprecisely defined syndrome labelled "poor neonatal adaptation" (PNAS).
Infants exposed to SRI medication and unexposed infants (with/without mothers with MDD) will be studied in terms of gestational age, birth weight & size, Apgar and Finnegan scores, respiratory distress, jitteriness, seizures and feeding problems, hypoglycemia and jaundice.Assessment of markers of psychiatric and endocrinological health care will allow for an extensive characterization of risk factors for and symptoms of PNAS, thereby improving safety and adherence to gold-standard treatment in MDD, allowing better management of women requiring antidepressant treatment during pregnancy.

E.2.2

Secondary objectives of the trial

Further objectives address how maternal depression severity, perceived stress, functioning scores, blood markers (metabolic, immuno-inflammatory, neuroplastic), anthropometric parameters, and psychosociodemographic and life-style factors moderate primary objectives;
how maternal depression scores during and after pregnancy will be moderated by perceived stress, blood markers (metabolic, immuno-inflammatory, neuroplastic), anthropometric parameters and personality; whether prenatal predictors (maternal depression severity, metabolic, immuno-inflammatory and neuroplastic markers, psychosociodemographic and life-style factors) of poor neonatal adaptation can be identified, specific to the SRI exposed group and for all infants; whether alternative definitions of poor neonatal adaptation based on registered symptoms can be identified.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

FOR MDD GROUPS

1. diagnosis of MDD according to ICD-10/DMS 5.0 criteria:
a current major depressive episode or a past episode within one year prior to pregnancy
2. age between 18 and 40 years
3. absence of any other lifetime primary psychiatric diagnosis except for comorbid anxiety disorders and personality disorders
4. absence of any severe non-psychiatric disorders and severe pregnancy complications
5. no drug use and no exposure to other neuropsychiatric medication than antidepressants at least one year prior to pregnancy
Exposure Group:
6.1 current treatment with SRI medication, starting at least at the second trimester of pregnancy (exposure ≥ 16 weeks, corresponding to 70% of pregnancy time after the 2nd trimester)
Non-Exposure Group:
6.2 no SRI treatment after the first trimester of pregnancy (in case of short exposure after the 2nd trimester: exposure ≤ 4 weeks, ending at least 2 weeks prior to delivery, is deemed acceptable)

FOR HEALTHY CONTROLS
1. absence of any lifetime psychiatric or severe non-psychiatric disorder
2. absence of any exposure to neuropsychiatric medication or drug use at least one year prior to pregnancy
3. age between 18 and 40 years
4. absence of any severe pregnancy complications

E.4

Principal exclusion criteria

see inclusion criteria

E.5 End points

E.5.1

Primary end point(s)

Early PNAS: according to total/itemwise Apgar
Continued PNAS according to total/itemwise Finnegan Score
Respiratory Distress: measured with respective items of Apgar & Finnegan Scores and clinical assessment
Admission to specializes care

E.5.1.1

Timepoint(s) of evaluation of this end point

VISIT 1: PRENATAL, 2ND TRIMESTER
1) Psychometric assessment
2) Laboratory chemistry parameters
3) Anthropometric parameters

VISIT 2: PRENATAL, 3RD TRIMESTER
1) Psychometric assessment
2) Laboratory chemistry
3) Anthropometric parameters

VISIT 3: POSTPARTUM, AT BIRTH
Neonatal Assessment: gestational age, birth weight and size, Apgar 6 Finnegan Scores , clinical symptoms

VISIT 4: POSTPARTUM, 2-4 WEEKS OF AGE
Neonatal Assessment: weight and size, Finnegan Score, clinical symptoms, air displacement plethysmography
Assessment of the mother: as performed at the 2nd prenatal visit, plus air displacement plethysmography

E.5.2

Secondary end point(s)

Gestational Age / Preterm Delivery
Weight & Size
Hypoglycemia, Jaundice by clinical assessment / blood glucose level
Jitteriness/Tremors, Seizures, Feeding Problems measured with the respective items of the Finnegan Score
Maternal Depression Severity by HAMD, EPDS & BDI-II

E.5.2.1

Timepoint(s) of evaluation of this end point

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

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)

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

E.8.1.1

Randomised

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

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

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

LVLS

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:

150

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

Yes

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

Yes

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

F.4 Planned number of subjects to be included

F.4.1

In the member state

150

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)

If required, patients will be treated according to routine protocols at the respective in- an outpatient departments of the University Clinics for Psychiatry and Psychotherapy and Gynecology.

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

2022-06-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2023-07-27

P. End of Trial
P.	End of Trial Status	Ongoing

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