Clozapine Induced Weight Gain

Weight Gain Clinical Trial

Official title:

Clozapine Induced Weight Gain: A Pharmacogenetic Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03996356
• Other study ID #: CT/688/000000/16
• Status: Not yet recruiting
• Start date: March 2020
• Est. completion date: October 2021

Study information

• Verified date: June 2019
• Source: Cwm Taf University Health Board (NHS)
• Contact: Brian P Tennant, PhD
• Phone: (+44)1685728278
• Email: brian.tennant[@]wales.nhs.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 160
• Est. completion date: October 2021
• Est. primary completion date: March 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Antipsychotic Agents
• Body Weight
• Pharmacogenetics
• Weight Gain

Intervention

Other:
• No study intervention - observational study
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.

Locations

Country	Name	City	State
United Kingdom	Cwm Taf University Health Board	Merthyr Tydfil	Wales

Sponsors (1)

Lead Sponsor	Collaborator
Cwm Taf University Health Board (NHS)

Country where clinical trial is conducted

United Kingdom, 

References & 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. Review. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. — View Citation

Mammès 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. — View Citation

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. Review. — View Citation

Ohlson LO, Larsson B, Svärdsudd K, Welin L, Eriksson H, Wilhelmsen L, Björntorp 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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Body-mass index (BMI)	BMI will be calculated by weight (kg)/ height^2 (m^2).	12 months
Primary	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
Primary	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	Blood haemoglobin A1c concentration	Haemoglobin A1c concentrations will be determined by ion-exchange HPLC (G8, Tosoh, Amsterdam, Netherlands)	6 months
Secondary	Waist:hip ratio	Waist:hip ratio will be calculated by waist circumference (cm)/hips circumference (cm)	12 months
Secondary	Lipid profile	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
Secondary	Clozapine side effects assessment by Clinical Global Impression (CGI) scale	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
Secondary	Clozapine:nor clozapine ratio	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