Clinical Trials Register

Summary
EudraCT Number:	2018-000178-31
Sponsor's Protocol Code Number:	TREATMENT-patients
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2018-03-02
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2018-000178-31

A.3

Full title of the trial

Metabolic Dysfunctions Associated with Pharmacological Treatment of Schizophrenia

Alteraciones metabólicas asociadas al tratamiento farmacológico de la esquizofrenia

A.3.1

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

Metabolic Dysfunctions Associated with Pharmacological Treatment of Schizophrenia

Alteraciones metabólicas asociadas al tratamiento farmacológico de la esquizofrenia

A.3.2

Name or abbreviated title of the trial where available

TREATMENT-patients

A.4.1

Sponsor's protocol code number

TREATMENT-patients

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	Fundación para la Investigación e Innovación Biosanitaria de Asturias (FINBA)
B.1.3.4	Country	Spain
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	Fundación para la Investigación e Innovación Biosanitaria de Asturias (FINBA)
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Instituto de Investigación Sanitaria del Hospital Universitario de La Princesa
B.5.2	Functional name of contact point	Yolanda Sanchez Carro
B.5.3	Address:
B.5.3.1	Street Address	Calle Diego de León, 62
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28006
B.5.3.4	Country	Spain
B.5.4	Telephone number	34658769786
B.5.5	Fax number	34915202425
B.5.6	E-mail	yolanda.sanchezc@uam.es

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	Olanzapine
D.2.1.1.2	Name of the Marketing Authorisation holder	-
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Olanzapine
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	OLANZAPINE
D.3.9.1	CAS number	132539-06-1
D.3.9.4	EV Substance Code	SUB09426MIG
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	5 to 20
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.IMP: 2
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	Aripiprazole
D.2.1.1.2	Name of the Marketing Authorisation holder	-
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Aripiprazole
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	ARIPIPRAZOLE
D.3.9.1	CAS number	129722-12-9
D.3.9.4	EV Substance Code	SUB05564MIG
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	10 to 30
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

Schizophrenia

Esquizofrenia

E.1.1.1

Medical condition in easily understood language

Schizophrenia

Esquizofrenia

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 know the molecular mechanisms associated with the metabolic effects of antipsychotics in order to identify markers with clinical predictive value in the face of metabolic dysfunction induced by antipsychotics

Conocer los mecanismos moleculares asociados con los efectos metabólicos de los antipsicóticos para poder identificar marcadores con valor predictivo clínico ante la disfunción metabólica inducida por antipsicóticos.

E.2.2

Secondary objectives of the trial

-To know the genetic polymorphisms and the genetic variants associated with an increased risk of metabolic dysfunction.
-To investigate the alterations of the mitochondrial physiology associated to the metabolic alterations induced by the antipsychotics.
-To know the alterations of RNA and proteins associated with the metabolic alterations induced by antipsychotics.
-Molecular alterations at the beginning of the treatment (at 72 hours, at the month and at 6 months after starting the treatment).

-Conocer los polimorfismos genéticos y las variantes genéticas asociadas a un mayor riesgo de disfunción metabólica.
-Conocer las alteraciones de la fisiología mitocondrial asociadas a las alteraciones metabólicas inducidas por los antipsicóticos.
-Conocer las alteraciones de RNA y proteínas asociadas a las alteraciones metabólicas inducidas por los antipsicóticos.
-Conocer las alteraciones moleculares al inicio del tratamiento (a las 72 horas, al mes y a los 6 meses de haber iniciado el tratamiento)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Informed consent signature
2.Age ≥18 years and <65 years.
3.First psychotic episode; the diagnosis of a current psychotic episode must be confirmed by the International Neuropsychiatric Interview (MINI) and correspond to one of these diagnoses of the group of schizophrenia and other psychotic disorders according to the international classification of diseases DSM-IV TR:
a.Schizophrenia (295.30, 295.10, 295.20, 295.90, 295.60)
b.Schizophreniform disorder (295.40)
c.Delusional disorder (297.1)
d.Brief Psychotic disorder (298.8)
e.Unespecified Psychosis (298.9)
f.Schizoaffective disorder (295.7)
g.Bipolar I disorder with psychotic features (296.02, 296.42, 296.55)
h.Major depressive disorder with psychotic features (296.23)
4.Not having taken any type of psychotropic drug in the period of one month prior to the first blood draw, with the exception of benzodiazepines.
5.Not having previously taken antipsychotic treatment.
6.Ability to understand and carry out correctly the development of the study

1. Firma del CI.
2. Edad igual o superior a 18 años e inferior a 65 años.
3. Primer episodio psicótico; el diagnóstico de episodio psicótico actual debe ser confirmado mediante la Entrevista Neuropsiquiatríca Internacional (MINI) y corresponderse con alguno de estos diagnósticos del grupo de la esquizofrenia y otros trastornos psicóticos según la clasificación internacional de enfermedades DSM-IV TR:
a. Esquizofrenia (295.30, 295.10, 295.20, 295.90, 295.60)
b. Trastorno esquizofreniforme (295.40)
c. Trastorno delirante (297.1)
d. Trastorno psicótico breve (298.8)
e. Trastorno psicótico no especificado (298.9)
f. Trastorno esquizoafectivo (295.7)
g. Trastorno bipolar I con síntomas psicóticos (296.02, 296.42, 296.55)
h. Trastorno depresivo mayor con síntomas psicóticos (296.23)
4. No haber tomado ningún tipo de psicofármaco en el periodo de un mes anterior a la primera extracción de sangre, con la excepción de benzodiacepinas.
5. No haber tomado previamente tratamiento antipsicótico.
6. Capacidad para comprender y llevar a cabo correctamente el desarrollo del estudio.

E.4

Principal exclusion criteria

1.Contraindications for treatment with olanzapine or aripiprazole
2.Electroconvulsive therapy in the current episode.
3.Psychopharmacological treatments (other than benzodiazepines) in the month prior to the inclusion of the study
4.During the study, the patient may only be in pharmacological treatment with one of the two antipsychotics under study (Olanzapine or Aripiprazole) and may only receive psychopharmacological treatment concomitant with the following benzodiazepines: dipotasic chloracepate and lormetazepam.
5.Subjects with a BMI outside the range 18.5-30.0.
6.Dependence or abuse of drugs (cannabis, opiates, cocaine or amphetamines) according to DSM-IVTR criteria. Patients may be included in which the use of drugs is sporadic and not usual
7.Alcohol consumption in the last month within the levels of risk to health (consumption ≥ 35 U / week in men and ≥ 21 U / week in women).
8.Women who are pregnant or breast-feeding.
9.Participation in another pharmacological research study in the previous 3 months.
10.Inability to understand information about the study.

1. Contraindicaciones para el tratamiento con Olanzapina o Aripiprazol.
2. Tratamiento electroconvulsivo en el episodio actual.
3. Tratamientos psicofarmacológicos (distintos a benzodiacepinas) en el mes anterior a la inclusión del estudio.
4. Durante el estudio el paciente sólo podrá estar en tratamiento farmacológico con uno de los dos antipsicóticos en estudio (Olanzapina o Aripiprazol) y únicamente podrá recibir tratamiento psicofarmacológico concomitante con las siguientes benzodiacepinas: cloracepato dipotasico y lormetazepam.
5. Sujetos con un IMC fuera del rango 18.5-30.0.
6. Dependencia o abuso de drogas (cannabis, opiáceos, cocaína o anfetaminas) según criterios DSM-IVTR. Podrán incluirse pacientes en los que el consumo de drogas sea esporádico y no habitual.
7. Consumo de alcohol en el último mes dentro de los niveles de riesgo para la salud (consumo ≥ 35 U/semana en hombres y ≥ 21 U/semana en mujeres).
8. Mujeres embarazadas o en periodo de lactancia.
9. Participación en otro estudio de investigación farmacológica en los 3 meses anteriores.
10. Incapacidad para comprender la información sobre el estudio.

E.5 End points

E.5.1

Primary end point(s)

Metabolic change induced by second generation antipsychotics, evaluated by changes observed in complete laboratory tests performed on patients:
-Glucose
-LDL cholesterol
-HDL cholesterol
-Total Cholesterol
-Triglycerides:
-Glycosylated Hemoglobin
-Bilirubin
-Transaminases AST / GOT
-ALT / GPT transaminases
-Insulin
-Peptide C
-TSH Profile TSH
Changes at the physiological level:
-Measurements in the BMI, abdominal perimeter and waist - hip index.
-Hepatic steatosis measured by the parameters obtained after performing a liver ecography: Liver Ecogeneity-Renal Cortex and the attenuation Index.
-Glucose tolerance index

Cambio metabólico inducido por antipsicóticos de segunda generación, evaluada mediante cambios observados en analítica completa realizada a los pacientes:
 Glucosa
 Colesterol LDL
 Colesterol HDL
 Colesterol Total
 Triglicéridos:
 Hemoglobina Glicosilada
 Bilirrubina
 Transaminasas AST/ GOT
 Transaminasas ALT/ GPT
 Insulina
 Péptido C
 Perfil Tiroideo TSH
Además de la medición de cambios a nivel fisiológico:
1. Mediciones en el IMC, perímetro abdominal e índice cintura – cadera.
2. Esteatosis hepática medida mediante los parámetros obtenidos tras la realización de una ecografía hepática, obteniéndose el Ratio Hepatorrenal: Ecogeneidad Hígado – Corteza renal y el Índice de Atenuación.
3. Índice de tolerancia a la glucosa

E.5.1.1

Timepoint(s) of evaluation of this end point

Six months

Seis meses

E.5.2

Secondary end point(s)

1.Isolation of DNA to know the genetic polymorphisms and the genetic variants associated with an increased risk of metabolic dysfunction.
2.Analysis of the mitochondrial activity to know the alterations of the mitochondrial physiology associated to the metabolic alterations induced by the antipsychotics.
3.RNA isolation and measurement of proteins to know the alterations of RNA and proteins associated with the metabolic alterations induced by antipsychotics.
4.Plasma concentration of the drug, to know the molecular alterations induced by the treatment (at 72 hours, at month and at 6 months after starting the treatment)

1. Aislamiento de ADN para conocer los polimorfismos genéticos y las variantes genéticas asociadas a un mayor riesgo de disfunción metabólica.
2. Análisis de la actividad mitocondrial para conocer las alteraciones de la fisiología mitocondrial asociadas a las alteraciones metabólicas inducidas por los antipsicóticos.
3. Aislamiento de ARN y medición de proteínas para conocer las alteraciones de ARN y proteínas asociadas a las alteraciones metabólicas inducidas por los antipsicóticos.
4. Concentración plasmática del fármaco: Olanzapina o Arpripazol para conocer las alteraciones moleculares inducidas por el tratamiento (a las 72 horas, al mes y a los 6 meses de haber iniciado el tratamiento)

E.5.2.1

Timepoint(s) of evaluation of this end point

Six months

Seis meses

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

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

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

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

Yes

E.8.1.2

Open

Yes

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

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

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)

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

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

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

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

No aplica

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

2018-05-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-04-12

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials