ANZCTR - Registration

The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01567124

Registration number

NCT01567124

Ethics application status

Date submitted

25/03/2012

Date registered

30/03/2012

Date last updated

24/04/2019

Titles & IDs

Public title

Alleviating the Metabolic Side Effects of Antipsychotic Medications

Scientific title

A Randomised Trial Examining the Effectiveness of Sympathetic Nervous Inhibition in Alleviating the Metabolic Side Effects of Antipsychotic Medications in Patients With Schizophrenia

Secondary ID [1]

1022794

Secondary ID [2]

108/12

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Schizophrenia

Condition category

Condition code

Mental Health

Schizophrenia

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Treatment: Drugs - Moxonidine
Treatment: Drugs - Placebo
Treatment: Drugs - Moxonidine
Treatment: Drugs - Placebo

Other: Olanzapine - Participants taking olanzapine at the time of recruitment will continue to take this medication as part of standard care for schizophrenia.

Other: Clozapine - Participants taking clozapine at the time of recruitment will continue to take this medication as part of standard care for schizophrenia.

Treatment: Drugs: Moxonidine
Participants who are randomly assigned to the moxonidine/experimental group will be treated with moxonidine oral tablets for twelve weeks. Participants will begin their moxonidine treatment at 0.2mg dosage, which will be increased to 0.4mg over the first two weeks.

At the end of the twelve weeks of treatment, participants will be withdrawn from moxonidine over a period of two weeks.

Treatment: Drugs: Placebo
To examine the effects of moxonidine treatment, a placebo oral tablet will be used for comparison purposes.

The duration and number of placebo tablets participants will be required to take will be the same as the amount required in the moxonidine group.

Treatment: Drugs: Moxonidine
Participants who are randomly assigned to the moxonidine/experimental group will be treated with moxonidine oral tablets for twelve weeks. Participants will begin their moxonidine treatment at 0.2mg dosage, which will be increased to 0.4mg over the first two weeks.

At the end of the twelve weeks of treatment, participants will be withdrawn from moxonidine over a period of two weeks.

Treatment: Drugs: Placebo
To examine the effects of moxonidine treatment, a placebo oral tablet will be used for comparison purposes.

The duration and number of placebo tablets participants will be required to take will be the same as the amount required in the moxonidine group.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

To determine the association between sympathetic nervous system and metabolic abnormalities (eg, weight gain) observed with antipsychotic treatment.

Timepoint [1]

Baseline and following 12 weeks of moxonidine/placebo treatment.

Secondary outcome [1]

Change from baseline in sympathetic nervous system activity.

Timepoint [1]

Baseline and following 12 weeks of moxonidine/placebo treatment.

Eligibility

Key inclusion criteria

* Aged 18-65 years.
* Capable of understanding and willing to provide signed and dated written, voluntary informed consent in advance of any protocol-specific procedures.
* Psychiatrist confirmed diagnosis of schizophrenia.
* Stabilised on clozapine or olanzapine for at least 6 weeks.
* 5% increase in body weight since commencement of clozapine or olanzapine.

Minimum age

18 Years

Maximum age

65 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

* Aged < 18 or > 65 years.
* On a Community Treatment Order (CTO).
* Comorbid mental health conditions including schizoaffective disorder, personality disorders, eating disorders, mental retardation, pervasive developmental disorder, delirium, dementia (ie, Mini Mental State Examination [MMSE] < 23), and amnesia.
* Concurrent treatment with two or more antipsychotics (including clozapine or olanzapine) at screening.
* Concomitant treatment with sedatives, tricyclic antidepressants, metformin, insulin or beta adrenergic blocking agents.
* Known or suspected hypersensitivity to moxonidine.
* Previous history of clozapine induced myocarditis.
* Pre-existing and/or current diagnosed heart disease.
* Comorbid medical conditions including medicated hypertension, bradycardia (heart rate < 50 beats/min), type 1 diabetes, epilepsy, bleeding disorders, alcohol/drug dependence, infectious blood diseases, and moderate-severe renal impairment.
* Clinically significant abnormalities on examination or laboratory testing, and clinically significant medical conditions not listed above that are serious and/or unstable.
* Pregnant or breastfeeding women.
* Women of childbearing potential (WOCP) who are not using medically accepted contraception (ie, intrauterine devices [IUDs], hormonal contraceptives [oral, depot, patch or injectable], and double barrier methods such as condoms or diaphragms with spermicidal gel or foam. Women who are postmenopausal (ie, amenorrhea for at least 12 consecutive months) or surgically sterile are not considered to be WOCP.
* Sexually active men with WOCP partners who are not using medically accepted contraception.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Phase 4

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Withdrawn

Data analysis

Reason for early stopping/withdrawal

Other reasons

Date of first participant enrolment

Anticipated

1/05/2012

Actual

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Ballarat Health Service Psychiatric Services - Ballarat

Recruitment hospital [2]

Monash Medical Centre - Monash Health - Clayton

Recruitment hospital [3]

Alfred and Baker Medical Unit - Alfred Hospital - Melbourne

Recruitment hospital [4]

Baker IDI Heart & Diabetes Institute - Melbourne

Recruitment postcode(s) [1]

- Ballarat

Recruitment postcode(s) [2]

- Clayton

Recruitment postcode(s) [3]

- Melbourne

Funding & Sponsors

Primary sponsor type

Other

Name

Baker Heart and Diabetes Institute

Address

Country

Other collaborator category [1]

Other

Name [1]

The Alfred

Address [1]

Country [1]

Other collaborator category [2]

Other

Name [2]

Monash Medical Centre

Address [2]

Country [2]

Other collaborator category [3]

Other

Name [3]

Ballarat Health Services

Address [3]

Country [3]

Ethics approval

Ethics application status

Summary

Brief summary

The use of antipsychotic medications has increased over the past decade. While more recently developed medications are improved with regards to extrapyramidal side effects, the use of atypical antipsychotics has been associated with substantial weight gain and a worsening of metabolic profile. The time course and extent of weight gain differs among antipsychotics, with olanzapine and clozapine being associated with greatest weight gain.

Mechanisms underlying a worsening metabolic profile, obesity and obesity-related illnesses are complex, extending beyond sedentary lifestyle, poor diet and genetic predisposition. There is also a growing body of evidence that the sympathetic nervous system (SNS) has a role in the generation of both obesity and obesity-related illness. While the role of the SNS in blood pressure control is readily acknowledged it is less well appreciated that activation of the SNS exerts profound metabolic effects.

Although the fact of a causal relation linking antipsychotic drugs and obesity is unequivocally established, the biological mechanisms operating are unclear, and strategies for preventive therapy remain largely unformulated.

This study aims to investigate the role of the SNS and its association with the metabolic abnormalities that are frequently observed in patients with schizophrenia following treatment with antipsychotic medications.

Additionally, the study will investigate whether treatment with the centrally acting sympatholytic agent moxonidine will modify SNS activity and, hence, favourably influence the downstream metabolic abnormalities seen in antipsychotic treated patients with schizophrenia.

Hypothesis 1: Elevated sympathetic nervous system activity underlies the metabolic disturbances observed in patients following antipsychotic therapy.

Aim 1: To investigate the role of the sympathetic nervous system and its association with the metabolic abnormalities that are frequently observed in patients with schizophrenia following treatment with antipsychotic medications

Hypothesis 2: Central sympathoinhibition with moxonidine will blunt the elevated sympathetic nervous activity and downstream metabolic abnormalities observed in antipsychotic treated patients with schizophrenia.

Aim 2: Determine whether treatment with the centrally acting sympatholytic agent moxonidine will modify sympathetic nervous system activity and, hence, favourably influence the downstream metabolic abnormalities seen in antipsychotic treated patients with schizophrenia.

Trial website

https://clinicaltrials.gov/study/NCT01567124

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Gavin Lambert

Address

Baker IDI Heart & Diabetes Institute

Country

Phone

Fax

Contact person for public queries

Name

Address

Country

Phone

Fax

Contact person for scientific queries

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT01567124

Trial Review

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01567124