Clinical Trials Register

Summary
EudraCT Number:	2021-004049-19
Sponsor's Protocol Code Number:	NL77938.018.23
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2024-09-13
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

Netherlands - Competent Authority

A.2

EudraCT number

2021-004049-19

A.3

Full title of the trial

Sodium oxybate as a potential new treatment for catatonia in patients with depression, bipolar disorder or a psychotic disorder, a randomized controlled trial. The Laborit study.

A.3.1

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

Sodium oxybate as a potential new treatment for catatonia in patients with depression, bipolar disorder or a psychotic disorder, a randomized controlled trial. The Laborit study.

A.4.1

Sponsor's protocol code number

NL77938.018.23

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	Amsterdam UMC
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	Amsterdam UMC
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	Amsterdam UMC
B.5.2	Functional name of contact point	sponsor
B.5.3	Address:
B.5.3.1	Street Address	Oldenaller 1
B.5.3.2	Town/ city	Amsterdam
B.5.3.3	Post code	1081 HJ
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	0031651830244
B.5.6	E-mail	e.vexel@amsterdamumc.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	No
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	sodium oxybate
D.3.4	Pharmaceutical form	Oral emulsion
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

Catatonia in patients with depression, bipolar disorder or a psychotic disorder

E.1.1.1

Medical condition in easily understood language

Catatonia in patients with depression, bipolar disorder or a psychotic disorder

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

To investigate whether sodium oxybate can be used as a novel treatment in psychiatric patients with catatonia, admitted to a psychiatric hospital. This randomized, controlled superiority trial will examine the effect of sodium oxybate on catatonia, compared to the effect of lorazepam. Study population: Patients with catatonia and a probable psychotic disorder, bipolar disorder or depressive disorder who do not respond to lorazepam, during 4 days of treatment with lorazepam.
Our primary objective is to determine if sodium oxybate is effective as a novel treatment in psychiatric patients with catatonia who are resistant to lorazepam, in a randomized controlled trial. This is obtained by comparing response to either high dose of lorazepam or sodium oxybate, after 4 days of treatment. Response is defined as a 50% reduction in symptoms based on the Bush Francis Catatonia Rating\ Scale (BFCRS).

E.2.2

Secondary objectives of the trial

1) To determine remission of catatonia, by comparing remission to either high dose of lorazepam or sodium oxybate, after 10 days of treatment. Remission is defined as a BFCRS score lower than 3 points or not fulfilling DSM 5 criteria for catatonia, i.e. 2 out of 12 classification criteria for catatonia.
2) To determine which side effects occur if sodium oxybate is administered in patients with catatonia, with an emphasis on oxygen levels, blood pressure, heart rate and vomiting, i.e. with regard to the risk to develop aspiration pneumonia.
3) To describe the acute course of catatonia, using an embedded cohort, alongside this RCT.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) Patients (age 18 and over) with catatonia with a DSM-5 classification of either unipolar depressive disorder, bipolar disorder or a psychotic disorder, admitted to an acute psychiatric ward, who do not respond to usual care (i.e., increasing doses of lorazepam to a maximum of 24 mg during 4 days).
2) The DSM-5 classification of catatonia, unipolar depressive disorder, bipolar disorder and psychotic disorder will be verified using the Mini-International Neuropsychiatric Interview module for the DSM-5, with the patients or with the patient’s caregiver; if a diagnosis cannot be classified with the MINI, then the clinical diagnosis from the medical record will be used.
3) Catatonia is present for a maximum of eight weeks.

E.4

Principal exclusion criteria

A potential subject who meets any of the following criteria will be excluded from participation in this study:
1) Not able to take drugs orally, i.e., subjects who actively resist treatment, and are thus not able/or want to take oral sodium oxybate.
2) Somatic disorder underlying catatonia.
3) Use of anti-psychotic drugs if patients prior to the development of catatonia either had an increase or change in anti-psychotic medication. This exclusion is necessary since most experts in the field of catatonia argue that catatonia in patients with an underlying psychotic disorder is either due to an increase in the dosage of anti-psychotic drugs or due to a change in anti-psychotic drugs, or due to not taking anti-psychotic drugs. We argue that the latter group should be allowed to be treated further with anti-psychotic medication if the patient’s treating psychiatrist deems this necessary and catatonia is mild, i.e. BFRCS <9.
4) Known heart failure or renal impairment due to significant amounts of sodium in the sodium- oxybate.
5) Known sleep apnoea.
6a) Use of GABAergic drugs including gabapentin, pregabalin and clonidine.
6b) Use of GHB dehydrogenase inhibitors, including valproate, phenytoin and ethosuximide. 6c) use of opioids, except tramadol
7) Presence of alcohol use disorder.
8) Presence of malignant catatonia (as is indicated by autonomic dysregulation, item 23 of the Bush Francis Catatonia rating scale, scoring 3 combined with moderately severe to severe muscle rigidity, item 11 of the Bush Francis Catatonia rating scale, scoring 2 or higher) or development of malignant catatonia during the study. Patients with malignant catatonia need to receive treatment with ECT as soon as possible since mortality in those with untreated catatonia ranges between 10 and 40%.

E.5 End points

E.5.1

Primary end point(s)

Response is defined as a 50% reduction in symptoms based on the Bush Francis Catatonia Rating Scale (BFCRS).

https://laborit-studie.nl/het-onderzoek/

E.5.1.1

Timepoint(s) of evaluation of this end point

Evaluation of the symptoms based on the Bush Francis Catatonia Rating Scale (BFCRS) will take place 3 times a day during 14 days.

E.5.2

Secondary end point(s)

Secondary end point:
Catatonia DSM-5 criteria
Side effects
Acute course of catatonia, using an embedded cohort, alongside this RCT.

E.5.2.1

Timepoint(s) of evaluation of this end point

Time points of evaluation:
Catatonia DSM-5 criteria at the end of the trial;
Side effects continuously;
Acute course of catatonia, using an embedded cohort, alongside this RCT.

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

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

Yes

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)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

lorazepam

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

Yes

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

End of the trial at:

42 inclusions, or
if more than 30% of patients using sodium oxybate are hospitalized in a general hospital because of respiratory insufficiency (Pa2<60mmHg), or
when more than 30% of patients using sodium oxybate develop malignant catatonia.

A one-time interim analysis for safety will be done when 21 participants are included and a preplanned interim analysis for futility.

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

At first, the patients treating psychiatrist will determine whether the patient can provide informed consent. In case a potential participant is not able to consent, written informed consent will be obtained from his or her legal representative.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

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)

Aside from tapering off the sodiumoxybate, plans of treatment of care will not differ from expected normal treatment.

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

2023-10-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-06-15

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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