Clinical Trials Register

Summary
EudraCT Number:	2013-000121-31
Sponsor's Protocol Code Number:	PSYK-TREAT-HEALTHY
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-03-21
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

Denmark - DHMA

A.2

EudraCT number

2013-000121-31

A.3

Full title of the trial

Does a GLP-1 receptor agonist change glucose tolerance in antipsychotic-treated patients?

Effekt af GLP-1 receptor agonisten liraglutid på glukosetolerance hos patienter i antipsykotisk behandling.

A.3.1

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

Does liraglutide (GLP-1 receptor agonist) change glucose tolerance in antipsychotic-treated patients?

Effekt af GLP-1 receptor agonisten liraglutid på glukosetolerance hos patienter i antipsykotisk behandling.

A.4.1

Sponsor's protocol code number

PSYK-TREAT-HEALTHY

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1128-3404

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	Prof., dr. med. Anders Fink-Jensen
B.1.3.4	Country
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	Novo Nordisk A/S
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Psykiatrisk Center København
B.5.2	Functional name of contact point	Psykiatrisk Afdeling O
B.5.3	Address:
B.5.3.1	Street Address	Edel Sauntes Allé 10
B.5.3.2	Town/ city	København Ø
B.5.3.3	Post code	2100
B.5.4	Telephone number	004538647072
B.5.5	Fax number	004538647077
B.5.6	E-mail	a.fink-jensen@dadlnet.dk

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	Victoza
D.2.1.1.2	Name of the Marketing Authorisation holder	Novo Nordisk A/S
D.2.1.2	Country which granted the Marketing Authorisation	Denmark
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	Solution for injection in pre-filled pen
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LIRAGLUTIDE
D.3.9.1	CAS number	204656-20-2
D.3.9.4	EV Substance Code	SUB25238
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	0.6 to 1.8
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	Suspension for injection in pre-filled pen
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Dysglycaemia, schizophrenia, paranoid psycosis, schizotypal disorder

Dysglykæmi, skizofreni, paranoid psykose, skizotypisk sindslidelse

E.1.1.1

Medical condition in easily understood language

Pre-diabetes in patients with a diagnosis of schizophrenia, paranoid psycosis or schizotypal disorder

Forstadier til sukkersyge hos patienter diagnosticeret med enten skizofreni, skizotypisk sindslidelse eller paranoid psykose

E.1.1.2

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.1
E.1.2	Level	LLT
E.1.2	Classification code	10036481
E.1.2	Term	Pre-diabetes
E.1.2	System Organ Class	100000004861

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 the effects of the GLP-1 receptor agonist Liraglutide 6.0 mg/mL, 3.0 mL pre-filled pen-injector (Victoza®) vs. Liraglutide placebo, 3.0 mL pre-filled pen-injector in psychiatric patient in treatment with clozapine or olanzapine.

Formålet med projektet er at undersøge, hvorvidt behandling med peptidet, liraglutid, der aktiverer GLP-1-receptoren, kan bedre dysglykæmien hos psykiatriske patienter i behandling med antipsykotisk medicin clozapin eller olanzapin.

E.2.2

Secondary objectives of the trial

Secondary objectives include changes of dysglycaemia (impaired fasting glucose (IFG), impaired glucose tolerance (IGT), combined IFG/IGT or diabetes), changes in body weight, waist circumference, blood pressure, secretion of incretin hormones, insulin sensitivity and beta cell function, evaluated by homeostatic model assessment (HOMA), DEXA scanning (body composition), lipid profile, liver function, dietary, exercise records and measures of psychopathology, alchohol use and quality of life. Identify differences in risk factors for diabetes between healthy controls and the participants. Also proteomic fingerprinting will be preformed. Furtermore, patients who have been included in the trial, will be approached 52 weeks after end of participation, in order to evaluate whether or not there is a long-term effect of the intervention in regrads to weight and metabolic disturbances.

Sekundære formål er at måle ændringer i dysglykæmien (impaired fasting glucose (IFG), impaired glucose tolerance (IGT), combined IFG/IGT or diabetes), vægt, taljemål, blodtryk, sekretion af inkretinhormonerne, insulinfølsomheden og beta-celle-funktionen, fedtfordelingen, lipid profilen, leverfunktionen, kost og motion, samt psykopatologi, alkoholforbrug og livskvalitet. Sammenligning af risikofaktorer for diabetes blandt vores patienter og raske kontroller, som får lavet baseline undersøgelserne. Analyse af metaboliske, hormonelle og immunologiske ubalancer i det perifere blod (proteomic fingerprinting). Ydermere vil deltagerne, som har været inkluderet i projektet få lavet en langtidsopfølgning et år efter endt deltagelse, for at undersøge om der er en vedvarende effekt af interventionen i forhold til vægt og metaboliske forstyrrelser.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

In our study, we allready collect blood samples of one hundred patients diagnosed with schizophrenia at week 0, 4, 8, 12, 16. One extra glass of 9 mL whole blood will be filled to preform proteomic fingerprinting. We wish to identify baseline metabolic, hormonal and immune imbalances among our participants. Furthermore, we wish to investigate, whether treatment with liraglutide possible could rebalance some of the metabolic, immune and hormonal disturbances, we expect to find at baseline.

We will enter into a scientific cooperation with Prof. Sabine Bahn and colleagues at the University of Cambridge, United Kingdom. Sabine Bahn and colleagues will perform all necessary analysis for proteomic profiling among our participants. We wish to do this, because identification of potential “hub” and “link” molecules in molecular pathways would be interest as further potential biomarkers or drug targets for schizophrenia

I vores studie tager vi allerede blodprøver i uge 0, 4, 8, 12, 16. Ved at fylde et ekstra glas med 9 mL fuldblod, vil vi være i stand til at identificere mulige metaboliske, hormonelle og immunologiske ubalancer blandt vores deltager ved baseline. Ydermere vil vi undersøge om 16 ugers behandling med liraglutid kan bedre disse ubalancer.

Vi vil indgå i et videnskabeligt samarbejde med Prof. Sabine Bahn og kollegaer på Cambridge Universitet i England. Sabine Bahn og kollegaer vil lave alle de nødvendige analyser. Vi ønsker at lave disse analyser for at identificere mulige "hub" eller "link" molekyler, som i fremtiden måske vil kunne bruges som biomarkører for skizofreni eller som mål for behandlingen.

E.3

Principal inclusion criteria

- Informed oral and written consent
- Diagnosed with schizophrenia, paranoid psychosis or schizotypal disorder according to the criteria of ICD10 (International Classification of Diseases, World Health Organization) or the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, the American Psychiatric Association)
- and on stable antipsychotic treatment with either clozapine or olanzapine for at least 6 months (without dose change for at least 30 days)
- Stable co-medications for at least 30 days.
- Age ≥18 years and ≤65 years
- Stable weight (defined as less than 5% change in weight over the last 3 month before inclusion)
- BMI ≥27 kg/m2
- Dysglycaemia:
1) HbA1c: 43 mmol/mol ≤ HbA1c ≤ 47 mmol/mol, or
2) Impaired fasting glucose (IFG): Fasting plasma glucose (FPG): 6.1 mmol/l ≤ FPG ≤ 6.9 mmol/l and HbA1c < 48 mmol/mol, or
3) Impaired glucose tolerance (IGT): two-hour plasma glucose after 75-g oral glucose tolerance test >7.8 mmol/l with a FPG < 7.0 mmol/l and HbA1c < 48 mmol/mol

- Informeret samtykke, mundtligt og skriftligt.
- Diagnosticeret med skizofreni, skizotypisk sindslidelse eller paranoid psykose i henhold til ICD-10 eller DSM-IV.
- Stabil behandling med clozapin eller olanzapin gennem 6 mdr. op til inklusion (uden ændring af dosis i 30 dage op til inklusion).
- Ingen ændringer i patientens øvrige medicin gennem 30 dage op til inklusion.
- Alder ≥18 år og ≤65 år.
- Stabil vægt (mindre end 5 % ændring over de sidste 3 mdr.).
- BMI ≥27 kg/m2
- Dysglykæmi
1. HbA1c: 43 mmol/mol ≤ HbA1c ≤ 47 mmol/mol eller
2. Fasteplasmaglukose (FPG): 6,1 mM til 6.9 mM og HbA1c < 48 mmol/mol eller
3. Plasmaglukose over 7,8 mM efter 75 g glukosebelastning forudgået af fasteplasmaglukose < 7,0 mM og HbA1c < 48 mmol/mol.

E.4

Principal exclusion criteria

- Compulsory treatment
- Females of child bearing potential who are pregnant, breast-feeding or have intention of becoming pregnant or are not using adequate contraceptive measures
- Subjects treated with corticosteroids or other hormone therapy (except estrogens)
- Any active substance abuse or dependence for the past 6 months (except for nicotine)
- Impaired hepatic function (liver transaminases >2 times upper normal limit)
- Impaired renal function (se-creatinine >150 μM and/or macroalbuminuria)
- Impaired pancreatic function (acute or chronic pancreatitis and/or amylase >2 times upper normal limit)
- Cardiac problems defined as decompensated heart failure (NYHA class III or IV), unstable angina pectoris and/or myocardial infarction within the last 12 months
- Uncontrolled hypertension (systolic blood pressure >180 mmHg, diastolic blood pressure >100 mmHg)
- Any condition that the investigator feels would interfere with trial participation
- Receiving any investigational drug within the last 3 months
- Use of weight-lowering pharmacotherapy within the preceding 3 month
- Type 1 or 2 diabetes HbA1c ≥ 48 mmol/mol or on treatment with antidiabetic medication

- Type 1 eller 2 diabetes med HbA1c ≥ 48 mmol/mol eller i behandling med diabetes medicin.
- Patienter i tvangsbehandling.
- Kvinder, som er gravide, ammer, eller som ønsker at blive gravide. Desuden kvinder, som ikke bruger relevant prævention.
- Behandling med steroid eller andre hormoner (undtagen østrogener).
- Misbrug eller afhængighed inden for de sidste 6 mdr. (fraset nikotinafhængighed).
- Nedsat leverfunktion (lever transaminaser >2 gange over normalområdet).
- Nedsat nyrefunktion (se-kreatinin >150 μM og/eller makroalbuminuri).
- Nedsat funktion af bugspytkirtlen (akut eller kronisk pancreatitis og/eller amylase >2 gange over normal området).
- Hjerteproblemer. Hjerteinsufficiens (NYHA III eller IV), ustabil angina pectoris og/eller AMI inden for 12 mdr.
- Svær hypertension (systolisk blodtryk >180 mmHg, diastolisk blodtryk >100 mmHg).
- Anden alvorlig sygdom, som kan få indflydelse for deltagelse i projektet.
- Patienter, som har været i behandling med forsøgsmedicin inden for 3 mdr. op til inklusion.
- Brug af slankemedicin inden for de sidste 3 mdr. op til inklusion.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is the change in glucose tolerance from baseline (measured by area under the curve (AUC) for the plasma glucose (PG) excursion following a 4-hour 75 g oral glucose tolerance test (OGTT)) to follow up at week 16 or to last observation if study participation is stopped earlier.

Det primære slutmål er at måle ændringer i glukosetolerancen (målt som arealet under kurven (AUC)) for plasma glukose (PG) efter en 4 timer 75 g oral sukkerbelastning (OGTT)) efter 16 ugers behandling eller til sidste kontrol, hvis deltageren ikke gennmfører alle 16 ugers behandling.

E.5.1.1

Timepoint(s) of evaluation of this end point

16 weeks

16 uger

E.5.2

Secondary end point(s)

Secondary end points include changes of dysglycaemia (impaired fasting glucose (IFG), impaired glucose tolerance (IGT), combined IFG/IGT or diabetes), changes in body weight, waist circumference, blood pressure, secretion of incretin hormones, insulin sensitivity and beta cell function, evaluated by homeostatic model assessment (HOMA), DEXA scanning (body composition), lipid profile, liver function, dietary, exercise records and measures of psychopathology, alchohol use and quality of life. Identify differences in risk factors for diabetes between healthy controls and the participants. Also proteomic fingerprinting will be preformed. Furthermore, patients who have been included in the trial, will be approached 52 weeks after end of participation, in order to evaluate whether or not there is a long-term effect of the intervention in regards to weight and metabolic disturbances.

Sekundære slutmål er at måle ændringer i dysglykæmien (impaired fasting glucose (IFG), impaired glucose tolerance (IGT), combined IFG/IGT or diabetes), vægt, taljemål, blodtryk, sekretion af inkretinhormonerne, insulinfølsomheden og beta-celle-funktionen, fedtfordelingen, lipid profilen, leverfunktionen, kost og motion, samt psykopatologi, alkoholforbrug og livskvalitet. Identificere forskelle i sygdomsmarkører for diabetes i mellem vores deltagere og raske kontroller. Ydermere vil der blive lavet analyser for metaboliske, immunologiske og hormonelle ubalancer (proteomic fingerprinting), og deltagerne, som har været inkluderet i projektet, vil få lavet en langtidsopfølgning et år efter endt deltagelse, for at undersøge om der er en vedvarende effekt af interventionen i forhold til metaboliske forstyrrelser og vægt.

E.5.2.1

Timepoint(s) of evaluation of this end point

16 weeks and 1 year

16 uger og 1 år

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

E.6.4

Safety

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

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

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

LVLS

Sidste patients sidste besøg

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:

100

F.1.3

Elderly (>=65 years)

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

F.3.3.7

Others

Yes

F.3.3.7.1

Details of other specific vulnerable populations

Severe mental illness

Svær psykiatrisk sygdom

F.4 Planned number of subjects to be included

F.4.1

In the member state

100

F.4.2

For a multinational trial

F.4.2.1

In the EEA

100

F.4.2.2

In the whole clinical trial

100

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)

None

Ingen

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Diabetologisk Forskningsafdeling, Gentofte Hospital
G.4.3.4	Network Country	Denmark
G.4 Investigator Network to be involved in the Trial: 2
G.4.1	Name of Organisation	Department of Endocrinology Research, Faculty of Health Sciences, University of Copenhagen
G.4.3.4	Network Country	Denmark

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2013-03-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-03-20

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-04-14

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