NCT03996356

Brief Summary

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
160

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started Mar 2020

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 20, 2019

Completed
4 days until next milestone

First Posted

Study publicly available on registry

June 24, 2019

Completed
8 months until next milestone

Study Start

First participant enrolled

March 1, 2020

Completed
1 year until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2021

Completed
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2021

Completed
Last Updated

June 24, 2019

Status Verified

June 1, 2019

Enrollment Period

1 year

First QC Date

June 20, 2019

Last Update Submit

June 21, 2019

Conditions

Weight GainAntipsychotic AgentsPharmacogenetics

Outcome Measures

Primary Outcomes (3)

  • Body-mass index (BMI)

    BMI will be calculated by weight (kg)/ height\^2 (m\^2).

    12 months

  • Leptin gene promoter region single nucleotide polymorphisms (SNPs) (rs7799039)

    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)

    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 Outcomes (5)

  • Blood haemoglobin A1c concentration

    6 months

  • Waist:hip ratio

    12 months

  • Lipid profile

    12 months

  • Clozapine side effects assessment by Clinical Global Impression (CGI) scale

    12 months

  • Clozapine:nor clozapine ratio

    12 months

Interventions

No study intervention - observational studyOTHER

This is an observational study where the comparative groups will be determined by the genetic variants (SNPs) of subjects and not an intervention, per se.

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability Sample
Study Population

Patients on clozapine treatment

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Cwm Taf University Health Board

Merthyr Tydfil, Wales, CF47 9DT, United Kingdom

Location

Related Publications (9)

  • 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.

    PMID: 10553730BACKGROUND

  • 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.

    PMID: 12518268BACKGROUND

  • 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.

    PMID: 11603885BACKGROUND

  • 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.

    PMID: 20463634BACKGROUND

  • 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.

    PMID: 11281277BACKGROUND

  • 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.

    PMID: 10215564BACKGROUND

  • 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.

    PMID: 4043554BACKGROUND

  • 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.

    PMID: 12086765BACKGROUND

  • 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.

    PMID: 12668355BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

4 blood samples to be taken at 0 and 6 months (2x EDTA plasma/whole blood, 2x serum). Biochemical markers and status of 2 common single nucleotide polymorphisms will be measured.

MeSH Terms

Conditions

Weight Gain

Condition Hierarchy (Ancestors)

Body Weight ChangesBody WeightSigns and SymptomsPathological Conditions, Signs and Symptoms

Study Officials

  • Brian P Tennant, PhD

    Cwm Taf Morgannwg UHB

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Brian P Tennant, PhD

CONTACT

(+44)1685728278brian.tennant@wales.nhs.uk

Rhian Beynon, MSc

CONTACT

01443444500rhian.beynon@wales.nhs.uk

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER GOV
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 20, 2019

First Posted

June 24, 2019

Study Start

March 1, 2020

Primary Completion

March 1, 2021

Study Completion

October 1, 2021

Last Updated

June 24, 2019

Record last verified: 2019-06

Locations

GB(1)