Ignite Creation Date:
2024-05-05 @ 11:06 PM
Last Modification Date:
2024-10-26 @ 10:29 AM
Study NCT ID:
NCT01259973
Status:
UNKNOWN
Last Update Posted:
2011-04-18
First Post:
2010-12-13
Brief Title:
Typical Versus Atypical Antipsychotics Occupation of Striatal Receptors and the Appearance of Extrapyramidal Symptomatology in Healthy Volunteers
Sponsor:
Hospital Clinic of Barcelona
Organization:
Hospital Clinic of Barcelona
Study Overview
Official Title:
Phase I Clinical Trial Study of the Impact of Pharmacogenetic Markers in Predicting the Appearance of Extrapyramidal Symptomatology After the Treatment With Typical vs Atypical Antipsychotics in Healthy Volunteers
Status:
UNKNOWN
Status Verified Date:
2011-01
Last Known Status:
ENROLLING_BY_INVITATION
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
APSEP
Brief 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-
Detailed Description:
Objective
The preliminary results indicate that pharmacological factors AP dose and drug availability depending on cytochrome activity are risk factors for AP-induced EPS
In this clinical trial the investigators will study in healthy volunteers the effects on pharmacokinetics occupancy of striatal dopaminergic receptors and the appearance of EPS according to genetic polymorphisms in cytochrome genes CYP2D6 3 4 5 6 and Nxn and CYP3A5 3 The investigators will compare a typical AP Haloperidol with an atypical AP Risperidone both of which are metabolized by CYP2D6 and CYP3A5
Specific objectives
Study the relationship between genetic polymorphisms in cytochrome genes CYP2D6 3 4 5 6 and Nxn and CYP3A5 3 and plasmatic levels of Haloperidol and Risperidone
Study the relationship between genetic polymorphisms in cytochrome genes CYP2D6 3 4 5 6 and Nxn and CYP3A5 3 and the grade of occupancy of striatal dopaminergic receptors with Haloperidol and Risperidone
Study the relationship between plasmatic levels of Haloperidol and Risperidone and the grade of occupancy of striatal dopaminergic receptors with these two drugs
Study the relationship between genetic polymorphisms in cytochrome genes CYP2D6 3 4 5 6 and Nxn and CYP3A5 3 plasmatic levels of Haloperidol and Risperidone and the grade of occupancy of striatal dopaminergic receptors with these two drugs with the appearance of AP-induced EPS
Methodology
From a cohort of 200 healthy volunteers males and females with ages between 18-30 years previously genotyped for CYP2D6 and CYP3A5 genes from January to June 2010 the investigators have selected subjects depending on their metabolizer phenotype poor metabolizers intermediate metabolizers extensive metabolizers and ultrarapid metabolizers by DNA extraction from whole blood samples and SNP detection approaches
Finally the investigators will include the following four phenotypical groups with 6-8 subjects in each of the groups a total of N32 subjects approximately
poor metabolizers PM CYP2D6
poor metabolizers PM CYP3A5
extensive metabolizers EM CYP2D6CYP3A
ultrarapid metabolizers UM CYP2D6
The design corresponds to a three ways cross-over randomized and double-blind trial with a wash-out period of one week among each treatment
Measurements of occupancy of striatal dopaminergic receptors will be done by single photon emission computed tomography -SPECT- and SEP will be measured based on the Simpson-Angus scale and actimetry
General protocol
One week before their participation in the trial volunteers will undergo clinical and physical explorations blood test electrocardiography urine drug screening and will be trained in the different tests of the study to minimize differences regarding to experience
During the study participants will be treated with a single dose of an AP drug 5mg Haloperidol or 25mg Risperidone or a single dose of placebo 25mL physiological serum
Plasma levels will be measured at 05h 1h 2h 4h 6h 8h and 12h of drugplacebo administration
The tracer 123IIBZM will be administered at 3h of drugplacebo administration and SPECT will be performed at 5h
Status of EPS as well as positive and negative AP-derived symptoms will be measured at -1h and at different time frames post-drugplacebo administration beginning at 3h and until 24h depending on each Scale used
Participants will be hospitalized for three complete days separated between them by one wash-out week after each treatment from 800h to 800h of the following day at Phase I Unit of Hospital de Sant Pau i de la Santa Creu in Barcelona in order to monitor the results obtained after each treatment During their hospitalization participants will be given food and drink every two hours
This clinical trial will start in February 2011 and finish in November 2011
The preliminary results indicate that pharmacological factors AP dose and drug availability depending on cytochrome activity are risk factors for AP-induced EPS
In this clinical trial the investigators will study in healthy volunteers the effects on pharmacokinetics occupancy of striatal dopaminergic receptors and the appearance of EPS according to genetic polymorphisms in cytochrome genes CYP2D6 3 4 5 6 and Nxn and CYP3A5 3 The investigators will compare a typical AP Haloperidol with an atypical AP Risperidone both of which are metabolized by CYP2D6 and CYP3A5
Specific objectives
Study the relationship between genetic polymorphisms in cytochrome genes CYP2D6 3 4 5 6 and Nxn and CYP3A5 3 and plasmatic levels of Haloperidol and Risperidone
Study the relationship between genetic polymorphisms in cytochrome genes CYP2D6 3 4 5 6 and Nxn and CYP3A5 3 and the grade of occupancy of striatal dopaminergic receptors with Haloperidol and Risperidone
Study the relationship between plasmatic levels of Haloperidol and Risperidone and the grade of occupancy of striatal dopaminergic receptors with these two drugs
Study the relationship between genetic polymorphisms in cytochrome genes CYP2D6 3 4 5 6 and Nxn and CYP3A5 3 plasmatic levels of Haloperidol and Risperidone and the grade of occupancy of striatal dopaminergic receptors with these two drugs with the appearance of AP-induced EPS
Methodology
From a cohort of 200 healthy volunteers males and females with ages between 18-30 years previously genotyped for CYP2D6 and CYP3A5 genes from January to June 2010 the investigators have selected subjects depending on their metabolizer phenotype poor metabolizers intermediate metabolizers extensive metabolizers and ultrarapid metabolizers by DNA extraction from whole blood samples and SNP detection approaches
Finally the investigators will include the following four phenotypical groups with 6-8 subjects in each of the groups a total of N32 subjects approximately
poor metabolizers PM CYP2D6
poor metabolizers PM CYP3A5
extensive metabolizers EM CYP2D6CYP3A
ultrarapid metabolizers UM CYP2D6
The design corresponds to a three ways cross-over randomized and double-blind trial with a wash-out period of one week among each treatment
Measurements of occupancy of striatal dopaminergic receptors will be done by single photon emission computed tomography -SPECT- and SEP will be measured based on the Simpson-Angus scale and actimetry
General protocol
One week before their participation in the trial volunteers will undergo clinical and physical explorations blood test electrocardiography urine drug screening and will be trained in the different tests of the study to minimize differences regarding to experience
During the study participants will be treated with a single dose of an AP drug 5mg Haloperidol or 25mg Risperidone or a single dose of placebo 25mL physiological serum
Plasma levels will be measured at 05h 1h 2h 4h 6h 8h and 12h of drugplacebo administration
The tracer 123IIBZM will be administered at 3h of drugplacebo administration and SPECT will be performed at 5h
Status of EPS as well as positive and negative AP-derived symptoms will be measured at -1h and at different time frames post-drugplacebo administration beginning at 3h and until 24h depending on each Scale used
Participants will be hospitalized for three complete days separated between them by one wash-out week after each treatment from 800h to 800h of the following day at Phase I Unit of Hospital de Sant Pau i de la Santa Creu in Barcelona in order to monitor the results obtained after each treatment During their hospitalization participants will be given food and drink every two hours
This clinical trial will start in February 2011 and finish in November 2011
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| TRA-065 | OTHER_GRANT | Dirección General de Terapias Avanzadas y Trasplantes Ministerio de Sanidad y Política Social | None |
| 2009-016519-40 | EUDRACT_NUMBER | None | None |