Patients Already Taking Risperidone for Clinical IndicationsNCT00395499
Measurement of Risperidone and 9-Hydroxyrisperidone in Plasma and Saliva
An observational study of Patients Already Taking Risperidone for Clinical Indications, run by Ohio State University at 2 sites in United States.
Trial summary
The purpose of this research is to: (1) examine the secrection of risperidone (RIS) (Risperdal) and its metabolite, 9-OH-RIS, in saliva, (2) determine the concentration ratio of RIS and 9-OH-RIS between plasma and saliva, and (3) compare the rate of decline in concentration of RIS and 9-OH-RIS in saliva and plasma by… Read more about this study
- Who is it for?
- Ages 4 to 14 years
- Conditions the study is for
- Patients Already Taking Risperidone for Clinical Indications
- What is being tested?
- Risperidone
- How many people
- 19 participants
- Where
- 2 sitesUnited States
- Study dates
- May 2001to Apr 2003
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 14 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- aged 4 to 14 years, inclusive
- male or female
- any type of psychiatric diagnosis
- maintained on risperidone monotherapy for at least four weeks
- no medication adjustments for the last two weeks
- must be taking risperidone on a twice daily (morning and evening) schedule.
Who cannot join
- significant medical condition (e.g., heart disease, hypertension, liver or renal failure, pulmonary disease, unstable seizure disorder)
- females of child-bearing potential who score positive of pregnancy test
- receiving concurrent medications that may either bind to or are a substrate for CYP 450 2D6 or inhibit/induce CYP 3A3/4 activity. These include: anti-HIV medications, azole antifungal medications, calcium channel antagonists, carbamazepine, cimetidine, macrolide antibiotics (erythromycin, clarithromycin), phenytoin, propoxyphene, rifampin, or tramadol.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
General Clinical Research Center
Columbus, Ohio, 43210
The Nisonger Center
Columbus, Ohio, 43210
About this study
The purpose of this research is to: (1) examine the secrection of risperidone (RIS) (Risperdal) and its metabolite, 9-OH-RIS, in saliva, (2) determine the concentration ratio of RIS and 9-OH-RIS between plasma and saliva, and (3) compare the rate of decline in concentration of RIS and 9-OH-RIS in saliva and plasma by measurements at timed intervals during a single dosing interval.
Read the detailed description
The purpose of this research is to: (1) examine the secrection of risperidone (RIS) (Risperdal) and its metabolite, 9-OH-RIS, in saliva, (2) determine the concentration ratio of RIS and 9-OH-RIS between plasma and saliva, and (3) compare the rate of decline in concentration of RIS and 9-OH-RIS in saliva and plasma by measurements at timed intervals during a single dosing interval.
RIS is a new atypical neuroleptic agent widely used in treatment of schizophrenia and related disorders. It is sometimes used in serious childhood disorders as well, such as autistic disorder. It has a beneficial effect on both positive and negative symptoms of schizophrenia, accompanied by a much lower incidence of adverse effects (e.g. parkinsonism, tardive dyskinesia, dystonias, neuroleptic malignant syndrome). RIS is also used as a treatment of children with pervasive developmental disorders (PDD). RIS is metabolized to 9-OH-RIS by hepatic CYP2D6 which exhibits genetic polymorphism. Since RIS and 9-OH-RIS are equally potent, the clinical significance of CYP 2D6 status is negligible. However, in extensive metabolizers (EM) the T(1/2) or RIS is about 3 hrs and taht of 9-OH-RIS is approximately 20 hrs. In poor metabolizers (PM) the half life of RIS is about 17 hrs and that of 9-OH-RIS 23 hrs.
Since compliance is a major problem in the management of schizophrenia, we are developing a rapid simplified test to measure RIS and 9-OH-RIS in salive and compare the concentration in samples of plasma collected concurrently. In this study, 12 adult patients (18 years and above) or minors (aged 5 to 17 years) already taking risperidone for clinical reasons will take their usual morning dose. Risperidone is usually administered once or twice a day.
At various intervals thereafter, a 1 to 2-milliliter specimen of saliva will be removed from the oral cavity by means of a syringe; in some cases it is more convenient to ask volunteers to expel saliva into a plastic cup. We will try to cover an 18-hour interval following dosing for the entire group (samples will be collected at 1/4, 1/2, 1, 2, 4, 8, 12, and 18 hours after taking the medicine. However, only some of the samples (2 or maximum of 3) will be gathered from any single patient. Following collection of saliva, a sample of 2 to 4 ml of blood will be withdrawn, and plasma will be separated and frozen. Saliva and plasma samples will gathered where the patient's drug concentrations would ordinarily be collected (e.g., Inpatient or Outpatient clinics, or phlebotomy laboratory). RIS concentrations will be measured by high pressure liquid chromatography (HPLC).
- Being tested
- Risperidone
- Keywords
- Risperidone, 9-Hydroxyrisperidone, Plasma, Saliva, children
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RisperidoneDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2006 (estimated)
- Study startMay 2001
- Study completionApr 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Patients Already Taking Risperidone for Clinical IndicationsStudies of the same condition, open and under way.
- More trials run by Ohio State UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Time perspective
- Prospective
- Enrolment
- 19 participants
Sponsor and investigators
- Lead sponsor
- Ohio State University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Michael Aman, Ohio State University
- Investigators
- Michael G. Aman, PhD, Principal investigator, Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00395499
- Sponsor's protocol ID
- 2000H0115
- Status last verified
- Jun 2016
- First submitted
- 2 Nov 2006
- Last updated
- 23 Jun 2016
- Results posted
- No
Publications
Aman MG, Paxton JW, Werry JS. Fluctuations in steady-state phenytoin concentrations as measured in saliva in children. Pediatr Pharmacol (New York). 1983;3(2):87-94.
PubMed 6674913Aman MG, Werry JS, Paxton JW, Turbott SH, Stewart AW. Effects of carbamazepine on psychomotor performance in children as a function of drug concentration, seizure type, and time of medication. Epilepsia. 1990 Jan-Feb;31(1):51-60. doi: 10.1111/j.1528-1157.1990.tb05360.x.
PubMed 2303013Aman MG, Werry JS, Paxton JW, Turbott SH. Effects of phenytoin on cognitive-motor performance in children as a function of drug concentration, seizure type, and time of medication. Epilepsia. 1994 Jan-Feb;35(1):172-80. doi: 10.1111/j.1528-1157.1994.tb02929.x.
PubMed 8112242Dumortier G, Lochu A, Zerrouk A, Van Nieuwenhuyse V, Colen de Melo P, Roche Rabreau D, Degrassat K. Whole saliva and plasma levels of clozapine and desmethylclozapine. J Clin Pharm Ther. 1998 Feb;23(1):35-40. doi: 10.1046/j.1365-2710.1998.00132.x.
PubMed 9756110Grant S, Fitton A. Risperidone. A review of its pharmacology and therapeutic potential in the treatment of schizophrenia. Drugs. 1994 Aug;48(2):253-73. doi: 10.2165/00003495-199448020-00009.
PubMed 7527327Haeckel R, Hanecke P. Application of saliva for drug monitoring. An in vivo model for transmembrane transport. Eur J Clin Chem Clin Biochem. 1996 Mar;34(3):171-91.
PubMed 8721405Lane HY, Chang WH. Risperidone-carbamazepine interactions: is cytochrome P450 3A involved? J Clin Psychiatry. 1998 Aug;59(8):430-1. No abstract available.
PubMed 9721825Lynn RK, Olsen GD, Leger RM, Gordon WP, Smith RG, Gerber N. The secretion of methadone and its major metabolite in the gastric juice of humans: comparison with blood and salivary concentrations. Drug Metab Dispos. 1976 Sep-Oct;4(5):504-9.
PubMed 10151Marder SR. Facilitating compliance with antipsychotic medication. J Clin Psychiatry. 1998;59 Suppl 3:21-5.
PubMed 9541334Nagasaki T, Ohkubo T, Sugawara K, Yasui N, Furukori H, Kaneko S. Determination of risperidone and 9-hydroxyrisperidone in human plasma by high-performance liquid chromatography: application to therapeutic drug monitoring in Japanese patients with schizophrenia. J Pharm Biomed Anal. 1999 Mar;19(3-4):595-601. doi: 10.1016/s0731-7085(98)00261-1.
PubMed 10704125Paxton JW, Aman MG, Werry JS. Fluctuations in salivary carbamazepine and carbamazepine-10,11-epoxide concentrations during the day in epileptic children. Epilepsia. 1983 Dec;24(6):716-24. doi: 10.1111/j.1528-1157.1983.tb04634.x.
PubMed 6641647Paxton JW, Donald RA. Enzyme immunoassay of carbamazepine in serum and saliva. J Pharmacol Methods. 1980 Jun;3(4):289-96. doi: 10.1016/0160-5402(80)90070-4. No abstract available.
PubMed 6993793Paxton JW, Whiting B, Stephen KW. Phenytoin concentrations in mixed, parotid and submandibular saliva and serum measured by radioimmunoassay. Br J Clin Pharmacol. 1977 Apr;4(2):185-91. doi: 10.1111/j.1365-2125.1977.tb00692.x.
PubMed 861132Walson PD, Mimaki T, Curless R, Mayersohn M, Perrier D. Once daily doses of phenobarbital in children. J Pediatr. 1980 Aug;97(2):303-5. doi: 10.1016/s0022-3476(80)80502-6. No abstract available.
PubMed 7400905Zuidema J, Hold KM, de Boer D, Maes RA. Saliva as a specimen for therapeutic drug monitoring in pharmacies. Pharm World Sci. 1996 Dec;18(6):193-4. doi: 10.1007/BF00735959. No abstract available.
PubMed 9010881
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Measurement of Risperidone and 9-Hydroxyrisperidone in Plasma and Saliva
- ClinicalTrials.gov ID
- NCT00395499
- Acronym / sponsor ID
- 2000H0115
- Keywords
- Risperidone, 9-Hydroxyrisperidone, Plasma, Saliva, children
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 19 participants
- Lead sponsor
- Ohio State UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- May 2001
- Study completion
- Apr 2003
- First posted
- 3 Nov 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research is to: (1) examine the secrection of risperidone (RIS) (Risperdal) and its metabolite, 9-OH-RIS, in saliva, (2) determine the concentration ratio of RIS and 9-OH-RIS between plasma and saliva, and (3) compare the rate of decline in concentration of RIS and 9-OH-RIS in saliva and plasma by measurements at timed intervals during a single dosing interval.
Detailed description
The purpose of this research is to: (1) examine the secrection of risperidone (RIS) (Risperdal) and its metabolite, 9-OH-RIS, in saliva, (2) determine the concentration ratio of RIS and 9-OH-RIS between plasma and saliva, and (3) compare the rate of decline in concentration of RIS and 9-OH-RIS in saliva and plasma by measurements at timed intervals during a single dosing interval.
RIS is a new atypical neuroleptic agent widely used in treatment of schizophrenia and related disorders. It is sometimes used in serious childhood disorders as well, such as autistic disorder. It has a beneficial effect on both positive and negative symptoms of schizophrenia, accompanied by a much lower incidence of adverse effects (e.g. parkinsonism, tardive dyskinesia, dystonias, neuroleptic malignant syndrome). RIS is also used as a treatment of children with pervasive developmental disorders (PDD). RIS is metabolized to 9-OH-RIS by hepatic CYP2D6 which exhibits genetic polymorphism. Since RIS and 9-OH-RIS are equally potent, the clinical significance of CYP 2D6 status is negligible. However, in extensive metabolizers (EM) the T(1/2) or RIS is about 3 hrs and taht of 9-OH-RIS is approximately 20 hrs. In poor metabolizers (PM) the half life of RIS is about 17 hrs and that of 9-OH-RIS 23 hrs.
Since compliance is a major problem in the management of schizophrenia, we are developing a rapid simplified test to measure RIS and 9-OH-RIS in salive and compare the concentration in samples of plasma collected concurrently. In this study, 12 adult patients (18 years and above) or minors (aged 5 to 17 years) already taking risperidone for clinical reasons will take their usual morning dose. Risperidone is usually administered once or twice a day.
At various intervals thereafter, a 1 to 2-milliliter specimen of saliva will be removed from the oral cavity by means of a syringe; in some cases it is more convenient to ask volunteers to expel saliva into a plastic cup. We will try to cover an 18-hour interval following dosing for the entire group (samples will be collected at 1/4, 1/2, 1, 2, 4, 8, 12, and 18 hours after taking the medicine. However, only some of the samples (2 or maximum of 3) will be gathered from any single patient. Following collection of saliva, a sample of 2 to 4 ml of blood will be withdrawn, and plasma will be separated and frozen. Saliva and plasma samples will gathered where the patient's drug concentrations would ordinarily be collected (e.g., Inpatient or Outpatient clinics, or phlebotomy laboratory). RIS concentrations will be measured by high pressure liquid chromatography (HPLC).
Study design
- Time perspective
- Prospective
Who may qualify
- Ages
- 4 to 14 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- aged 4 to 14 years, inclusive
- male or female
- any type of psychiatric diagnosis
- maintained on risperidone monotherapy for at least four weeks
- no medication adjustments for the last two weeks
Key exclusion criteria (3 listed)
- significant medical condition (e.g., heart disease, hypertension, liver or renal failure, pulmonary disease, unstable seizure disorder)
- females of child-bearing potential who score positive of pregnancy test
- receiving concurrent medications that may either bind to or are a substrate for CYP 450 2D6 or inhibit/induce CYP 3A3/4 activity. These include: anti-HIV medications, azole antifungal medications, calcium channel antagonists, carbamazepine, cimetidine, macrolide antibiotics (erythromycin, clarithromycin), phenytoin, propoxyphene, rifampin, or tramadol.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Risperidone | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2016.
- Background: PubMed 6674913Aman MG, Paxton JW, Werry JS. Fluctuations in steady-state phenytoin concentrations as measured in saliva in children. Pediatr Pharmacol (New York). 1983;3(2):87-94.
- Background: PubMed 2303013Aman MG, Werry JS, Paxton JW, Turbott SH, Stewart AW. Effects of carbamazepine on psychomotor performance in children as a function of drug concentration, seizure type, and time of medication. Epilepsia. 1990 Jan-Feb;31(1):51-60. doi: 10.1111/j.1528-1157.1990.tb05360.x.
- Background: PubMed 8112242Aman MG, Werry JS, Paxton JW, Turbott SH. Effects of phenytoin on cognitive-motor performance in children as a function of drug concentration, seizure type, and time of medication. Epilepsia. 1994 Jan-Feb;35(1):172-80. doi: 10.1111/j.1528-1157.1994.tb02929.x.
- Background: PubMed 9756110Dumortier G, Lochu A, Zerrouk A, Van Nieuwenhuyse V, Colen de Melo P, Roche Rabreau D, Degrassat K. Whole saliva and plasma levels of clozapine and desmethylclozapine. J Clin Pharm Ther. 1998 Feb;23(1):35-40. doi: 10.1046/j.1365-2710.1998.00132.x.
- Background: PubMed 7527327Grant S, Fitton A. Risperidone. A review of its pharmacology and therapeutic potential in the treatment of schizophrenia. Drugs. 1994 Aug;48(2):253-73. doi: 10.2165/00003495-199448020-00009.
- Background: PubMed 8721405Haeckel R, Hanecke P. Application of saliva for drug monitoring. An in vivo model for transmembrane transport. Eur J Clin Chem Clin Biochem. 1996 Mar;34(3):171-91.
- Background: PubMed 9721825Lane HY, Chang WH. Risperidone-carbamazepine interactions: is cytochrome P450 3A involved? J Clin Psychiatry. 1998 Aug;59(8):430-1. No abstract available.
- Background: PubMed 10151Lynn RK, Olsen GD, Leger RM, Gordon WP, Smith RG, Gerber N. The secretion of methadone and its major metabolite in the gastric juice of humans: comparison with blood and salivary concentrations. Drug Metab Dispos. 1976 Sep-Oct;4(5):504-9.
- Background: PubMed 9541334Marder SR. Facilitating compliance with antipsychotic medication. J Clin Psychiatry. 1998;59 Suppl 3:21-5.
- Background: PubMed 10704125Nagasaki T, Ohkubo T, Sugawara K, Yasui N, Furukori H, Kaneko S. Determination of risperidone and 9-hydroxyrisperidone in human plasma by high-performance liquid chromatography: application to therapeutic drug monitoring in Japanese patients with schizophrenia. J Pharm Biomed Anal. 1999 Mar;19(3-4):595-601. doi: 10.1016/s0731-7085(98)00261-1.
- Background: PubMed 6641647Paxton JW, Aman MG, Werry JS. Fluctuations in salivary carbamazepine and carbamazepine-10,11-epoxide concentrations during the day in epileptic children. Epilepsia. 1983 Dec;24(6):716-24. doi: 10.1111/j.1528-1157.1983.tb04634.x.
- Background: PubMed 6993793Paxton JW, Donald RA. Enzyme immunoassay of carbamazepine in serum and saliva. J Pharmacol Methods. 1980 Jun;3(4):289-96. doi: 10.1016/0160-5402(80)90070-4. No abstract available.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael G. Aman, PhD principal investigator
Ohio State University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Patients Already Taking Risperidone for Clinical Indications, run by Ohio State University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00395499, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2016.