- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03996356
Clozapine Induced Weight Gain
June 21, 2019 updated by: Cwm Taf University Health Board (NHS)
Clozapine Induced Weight Gain: A Pharmacogenetic Study
Clozapine is prescribed to patients with psychosis in whom other treatments have not worked.
Research has shown, however, that clozapine may be associated with weight gain and abnormal blood sugar levels in some patients.
There is strong evidence to suggest that genetic variation between individuals plays an important role in the development of these side effects in response to the medication.
Our research aims to evaluate the effects of two genes and the blood level of clozapine on side-effects such as weight changes and blood sugar levels in patients receiving clozapine treatment.
From out-patient clinics in Cwm Taf UHB, the investigators aim to recruit 160 patients who are taking clozapine; collect information/ measurements from recruits relating to size/ weight/ BMI, risk of diabetes and blood samples to measure markers of blood sugar, fat/lipids, clozapine and its breakdown products, blood cells and variants of two specific genes.
From this information the investigators will be particularly interested to understand if there is any association between the variation in these two genes with weight gain or changes in blood sugar, in patients taking clozapine.
Study Overview
Status
Unknown
Conditions
Intervention / Treatment
Study Type
Observational
Enrollment (Anticipated)
160
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Brian P Tennant, PhD
- Phone Number: (+44)1685728278
- Email: brian.tennant@wales.nhs.uk
Study Contact Backup
- Name: Rhian Beynon, MSc
- Phone Number: 01443444500
- Email: rhian.beynon@wales.nhs.uk
Study Locations
-
-
Wales
-
Merthyr Tydfil, Wales, United Kingdom, CF47 9DT
- Cwm Taf University Health Board
-
Contact:
- Rhian Beynon, MSc
- Phone Number: 01443444500
- Email: rhian.beynon@wales.nhs.uk
-
Contact:
- Brian P Tennant, PhD
- Phone Number: (44)1685728278
- Email: brian.tennant@wales.nhs.uk
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Sampling Method
Probability Sample
Study Population
Patients on clozapine treatment
Description
Inclusion Criteria:
- Age 18 years or over
- Taking/compliant with clozapine antipsychotic medications.
- Patients meeting the ICD-10 criteria for a diagnosis of schizophrenia, schizoaffective or borderline personality disorders.
Exclusion Criteria:
- History of current alcohol/illicit substance dependency.
- Unable/ unsuitable to complete the study protocol e.g. acutely ill, suicidal or aggressive patients.
- Unable to consent to the study.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Body-mass index (BMI)
Time Frame: 12 months
|
BMI will be calculated by weight (kg)/ height^2 (m^2).
|
12 months
|
Leptin gene promoter region single nucleotide polymorphisms (SNPs) (rs7799039)
Time Frame: 12 months
|
SNPs will be determined by polymerase chain reaction followed by restriction fragment length polymorphism analysis to determine (c.-2548G or c.-2548A) .
|
12 months
|
Serotonin 5-HT 2C receptor gene single nucleotide polymorphisms (SNPs) (rs3813929)
Time Frame: 12 months
|
SNPs will be determined by polymerase chain reaction followed by restriction fragment length polymorphism analysis to determine (c.-759C or c.-759T) .
|
12 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Blood haemoglobin A1c concentration
Time Frame: 6 months
|
Haemoglobin A1c concentrations will be determined by ion-exchange HPLC (G8, Tosoh, Amsterdam, Netherlands)
|
6 months
|
Waist:hip ratio
Time Frame: 12 months
|
Waist:hip ratio will be calculated by waist circumference (cm)/hips circumference (cm)
|
12 months
|
Lipid profile
Time Frame: 12 months
|
Serum lipid profiles will include total cholesterol, HDL cholesterol, LDL cholesterol and triglyceride.
These will be measured by enzymatic colorimetric methods on cobas-Roche analysers (Roche, Burges Hill, UK) except LDL cholesterol, which will be calculated using the Friedewald equation ([LDL cholesterol] = [Total cholesterol] - ([Triglyceride] / 2.2) - [HDL cholesterol]
|
12 months
|
Clozapine side effects assessment by Clinical Global Impression (CGI) scale
Time Frame: 12 months
|
Clinical Global Impression (CGI) scale is a validated tool to assess clozapine side effects (Ref: Guy W, editor.
ECDEU Assessment Manual for Psychopharmacology.
1976.
Rockville,MD, U.S. Department of Health, Education, and Welfare)
|
12 months
|
Clozapine:nor clozapine ratio
Time Frame: 12 months
|
Clozapine:nor clozapine ratio is calculated by clozapine (ug/L)/ nor clozapine (ug/L) both measured by high-performance liquid chromatography with diode-array detection.
|
12 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Brian P Tennant, PhD, Cwm Taf Morgannwg UHB
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Allison DB, Mentore JL, Heo M, Chandler LP, Cappelleri JC, Infante MC, Weiden PJ. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry. 1999 Nov;156(11):1686-96. doi: 10.1176/ajp.156.11.1686.
- Baptista T, Kin NM, Beaulieu S, de Baptista EA. Obesity and related metabolic abnormalities during antipsychotic drug administration: mechanisms, management and research perspectives. Pharmacopsychiatry. 2002 Nov;35(6):205-19. doi: 10.1055/s-2002-36391.
- Basile VS, Masellis M, McIntyre RS, Meltzer HY, Lieberman JA, Kennedy JL. Genetic dissection of atypical antipsychotic-induced weight gain: novel preliminary data on the pharmacogenetic puzzle. J Clin Psychiatry. 2001;62 Suppl 23:45-66.
- Couchman L, Morgan PE, Spencer EP, Flanagan RJ. Plasma clozapine, norclozapine, and the clozapine:norclozapine ratio in relation to prescribed dose and other factors: data from a therapeutic drug monitoring service, 1993-2007. Ther Drug Monit. 2010 Aug;32(4):438-47. doi: 10.1097/FTD.0b013e3181dad1fb.
- Mammes O, Betoulle D, Aubert R, Herbeth B, Siest G, Fumeron F. Association of the G-2548A polymorphism in the 5' region of the LEP gene with overweight. Ann Hum Genet. 2000 Sep;64(Pt 5):391-4. doi: 10.1017/s0003480000008277.
- Mantzoros CS. The role of leptin in human obesity and disease: a review of current evidence. Ann Intern Med. 1999 Apr 20;130(8):671-80. doi: 10.7326/0003-4819-130-8-199904200-00014.
- Ohlson LO, Larsson B, Svardsudd K, Welin L, Eriksson H, Wilhelmsen L, Bjorntorp P, Tibblin G. The influence of body fat distribution on the incidence of diabetes mellitus. 13.5 years of follow-up of the participants in the study of men born in 1913. Diabetes. 1985 Oct;34(10):1055-8. doi: 10.2337/diab.34.10.1055.
- Reynolds GP, Zhang ZJ, Zhang XB. Association of antipsychotic drug-induced weight gain with a 5-HT2C receptor gene polymorphism. Lancet. 2002 Jun 15;359(9323):2086-7. doi: 10.1016/S0140-6736(02)08913-4.
- Reynolds GP, Zhang Z, Zhang X. Polymorphism of the promoter region of the serotonin 5-HT(2C) receptor gene and clozapine-induced weight gain. Am J Psychiatry. 2003 Apr;160(4):677-9. doi: 10.1176/appi.ajp.160.4.677.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Anticipated)
March 1, 2020
Primary Completion (Anticipated)
March 1, 2021
Study Completion (Anticipated)
October 1, 2021
Study Registration Dates
First Submitted
June 20, 2019
First Submitted That Met QC Criteria
June 21, 2019
First Posted (Actual)
June 24, 2019
Study Record Updates
Last Update Posted (Actual)
June 24, 2019
Last Update Submitted That Met QC Criteria
June 21, 2019
Last Verified
June 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CT/688/000000/16
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Weight Gain
-
Andalas UniversityNational Institute of Health Research and Development, Ministry of Health...CompletedBirth Weight | Pregnancy Weight GainIndonesia
-
Western University, CanadaIowa State UniversityCompletedBirth Weight | Excessive Weight Gain in Pregnancy With Baby Delivered | Excessive Weight Gain in Pregnancy, First TrimesterCanada
-
University of PittsburghThe Obesity Society; Weight Watchers InternationalCompletedObesity | Weight Gain, Maternal | Postpartum Weight RetentionUnited States
-
Medical University of South CarolinaNational Center for Research Resources (NCRR)Terminated
-
T.C. ORDU ÜNİVERSİTESİEge UniversityCompletedGestational Weight GainTurkey
-
University of HawaiiCompletedGestational Weight GainUnited States
-
Helena PiccininiNova Scotia Health AuthorityWithdrawnGestational Weight GainCanada
-
West China HospitalWest China Second University HospitalCompleted
-
Corcept TherapeuticsEli Lilly and CompanyCompletedWeight-Gain PreventionIndia
-
University of Colorado, DenverEunice Kennedy Shriver National Institute of Child Health and Human Development...Completed
Clinical Trials on No study intervention - observational study
-
Drexel UniversityCompletedOsteoporosisUnited States
-
The Aurum Institute NPCKarolinska Institutet; Ludwig-Maximilians - University of Munich; University... and other collaboratorsUnknownRespiratory Tract Infections | Tuberculosis, PulmonaryMozambique, South Africa, Tanzania, Gambia
-
Hospital Universitario La Paz3MVX CCB and Agaplesion Markus Krankenhaus, Frankfurt a.M., Germany.; Department...RecruitingEmbolism | Atrial Fibrillation | Arrhythmia | Stroke, Acute | Stroke Sequelae | AblationSpain
-
Liverpool School of Tropical MedicineLondon School of Hygiene and Tropical Medicine; Wellcome Trust; University of... and other collaboratorsRecruitingKidney Diseases | Chronic Kidney Diseases | Non-communicable Disease | Non-Communicable Chronic DiseasesMalawi
-
Nanfang Hospital of Southern Medical UniversityThe First Affiliated Hospital of Anhui Medical University; Xiangya Hospital... and other collaboratorsRecruiting
-
RenJi HospitalNot yet recruitingEnd Stage Renal Disease on DialysisChina
-
Nanowear Inc.RecruitingElective Surgical ProceduresUnited States
-
Sheffield Teaching Hospitals NHS Foundation TrustNational Institute for Health Research, United Kingdom; Alexion Pharmaceuticals...Completed
-
Manchester University NHS Foundation TrustUniversity of Oxford; University of LiverpoolCompletedPremature Birth | Enterocolitis, Necrotizing | Gastroschisis | Meconium Ileus | Bowel Obstruction | Atresia; Bowel | Perforation BowelUnited Kingdom
-
Gérard AmarencoCompletedLower Urinary Tract Symptoms | Intermittent Urethral Catheterization | Treatment Adherence | Patient SatisfactionFrance