Typical Versus Atypical Antipsychotics; Occupation of Striatal Receptors and the Appearance of Extrapyramidal Symptomatology, in Healthy Volunteers

• Status: Unknown status
• Trial end date: 2011-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to determine in healthy volunteers treated with typical or atypical antipsychotics -AP-, the relationship between genetic polymorphisms in cytochrome genes CYP2D6 (*3, *4, *5, *6 and Nxn) and CYP3A5 (*3) with antipsychotic pharmacokinetics, occupancy of striatal dopaminergic receptors and the appearance of extrapyramidal symptomatology -EPS-.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Hospital Clinic of Barcelona
• Collaborators: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau; Fundacion Clinic per a la Recerca Biomédica; University of Barcelona
• Treatments: Antipsychotic Agents; Haloperidol; Haloperidol decanoate; Risperidone

Criteria

Inclusion Criteria that chosen participants must fulfill:

1. Subjects of both genders with ages between 18-30 years.

2. Subjects with normal values of clinical history and physical exploration.

3. Subjects without evidence of significant disease, organic or psychiatric, according to anamnesis (medical history), physical exploration and complementary tests.

4. Subjects with normal values of laboratory tests (hemogram and biochemical tests).

5. Subjects with normal values of vital signs (Blood pressure, Heart rate, Temperature) and Electrocardiography.

6. Female subjects must be using safe contraceptive methods, different from oral contraceptives.

7. Subjects could not have taken part in other clinical trials during the three previous months before to the beginning of this study.

8. Subjects could not have given blood during four weeks before the beginning of this study.

9. Subjects must accept freely their participation, with written informed consent.

10. After previous genotyping for CYP2D6 and CYP3A4/A5 genes, chosen participants must have one of the following genotypes of interest for this study:

• poor metabolizers (PM) CYP2D6*

• poor metabolizers (PM) CYP3A5**

• extensive metabolizers (EM) CYP2D6/CYP3A

• ultrarapid metabolizers (UM) CYP2D6*

11. Subjects must accept to undergo neuroimaging (SPECT).

Exclusion Criteria to reject potential participants:

1. Subjects with previous medical history of alcoholism or drug dependency.

2. Subjects with clinical history of allergy, idiosyncrasy or hypersensitivity to drugs.

3. Subjects with clinical history or current treatment with drugs whose metabolism could interfere in the action of CYP2D6 and CYP3A5 cytochromes, particularly if they are not able to give up the treatment for a period of 3-4 weeks before the beginning of the study and during its execution.

4. Subjects with clinical history or current consumption of drugs that could interfere in the action of CYP2D6 and CYP3A5 cytochromes (St John's wort, cruciferae, grapefruit ...), particularly if they are not able to give up their consumption for a period of 3-4 weeks before the beginning of the study and during its execution.

5. Subjects with contraindications for antipsychotic treatments due to: familiar/clinical history of hypersensitivity to antipsychotic drugs, deep depression of central nervous system, coma, Parkinson's disease.

6. Pregnant women, women in breastfeeding period or women that do not use safe contraceptive methods, different from oral contraception.

7. Subjects with positive serology for hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV).

8. Subjets with positive test in urine for ethanol, cannabis, cocaine, amphetamines, benzodiazepines and/or opiates.