Alleviating the Metabolic Side Effects of Antipsychotic Medications

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Baker IDI Heart and Diabetes Institute
Sponsor:
Collaborators:
The Alfred
Monash Medical Centre
Ballarat Health Service Psychiatric Services
Information provided by (Responsible Party):
Baker IDI Heart and Diabetes Institute
ClinicalTrials.gov Identifier:
NCT01567124
First received: March 25, 2012
Last updated: December 16, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Drug: Moxonidine
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomised Trial Examining the Effectiveness of Sympathetic Nervous Inhibition in Alleviating the Metabolic Side Effects of Antipsychotic Medications in Patients With Schizophrenia

Resource links provided by NLM:


Further study details as provided by Baker IDI Heart and Diabetes Institute:

Primary Outcome Measures:
  • To determine the association between sympathetic nervous system and metabolic abnormalities (eg, weight gain) observed with antipsychotic treatment. [ Time Frame: Baseline and following 12 weeks of moxonidine/placebo treatment. ] [ Designated as safety issue: No ]
    To investigate the role of the sympathetic nervous system and it's association with the metabolic abnormalities that are frequently observed in patients with schizophrenia who are treated with antipsychotic medications; namely clozapine and olanzapine.


Secondary Outcome Measures:
  • Change from baseline in sympathetic nervous system activity. [ Time Frame: Baseline and following 12 weeks of moxonidine/placebo treatment. ] [ Designated as safety issue: Yes ]
    We will explore whether treatment with the centrally acting sympatholytic agent, moxonidine, modifies sympathetic nervous system activity and hence, has a favourable influence on the downstream metabolic abnormalities seen in schizophrenic patients treated with antipsychotics.


Estimated Enrollment: 90
Study Start Date: May 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Olanzapine
Participants taking olanzapine at the time of recruitment will continue to take this medication as part of standard care for schizophrenia.
Drug: 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.

Other Name: Physiotens
Drug: 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.

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

Other Name: Physiotens
Drug: 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.


  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01567124

Contacts
Contact: Sarah Tremethick +61 3 8532 1145 sarah.tremethick@bakeridi.edu.au
Contact: Jennifer Grigo +61 3 8532 1166 jennifer.grigo@bakeridi.edu.au

Locations
Australia, Victoria
Ballarat Health Service Psychiatric Services Recruiting
Ballarat, Victoria, Australia
Principal Investigator: Abdul Khalid         
Sub-Investigator: Rajul Tandon         
Sub-Investigator: Sonia Ghai         
Sub-Investigator: Arup Dhar         
Sub-Investigator: Sarah Tremethick         
Sub-Investigator: Jennifer Grigo         
Sub-Investigator: Pella Karalis         
Monash Medical Centre - Monash Health Recruiting
Clayton, Victoria, Australia
Principal Investigator: David Barton         
Sub-Investigator: Arup Dhar         
Sub-Investigator: Sarah Tremethick         
Sub-Investigator: Jennifer Grigo         
Sub-Investigator: Krishna Vaddadi         
Alfred and Baker Medical Unit - Alfred Hospital Recruiting
Melbourne, Victoria, Australia
Principal Investigator: Gavin Lambert         
Sub-Investigator: Markus Schlaich         
Sub-Investigator: Elisabeth Lambert         
Sub-Investigator: Murray Esler         
Sub-Investigator: Geoff Head         
Sub-Investigator: Dagmara Hering         
Sub-Investigator: Nina Eikelis         
Sub-Investigator: Carolina Ika Sari         
Sub-Investigator: Petra Marusic         
Sub-Investigator: Toni Rice         
Sub-Investigator: Mariee Grima         
Sub-Investigator: David Barton         
Sub-Investigator: Arup Dhar         
Sub-Investigator: Sarah Tremethick         
Sub-Investigator: Nora Straznicky         
Sub-Investigator: John Dixon         
Sub-Investigator: Jennifer Grigo         
Sub-Investigator: Donna Vizi         
Sub-Investigator: Louise Hammond         
Baker IDI Heart & Diabetes Institute Recruiting
Melbourne, Victoria, Australia
Principal Investigator: Gavin Lambert         
Sub-Investigator: Markus Schlaich         
Sub-Investigator: Elisabeth Lambert         
Sub-Investigator: Murray Esler         
Sub-Investigator: Geoff Head         
Sub-Investigator: Dagmara Hering         
Sub-Investigator: Nina Eikelis         
Sub-Investigator: Carolina Ika Sari         
Sub-Investigator: Petra Marusic         
Sub-Investigator: Toni Rice         
Sub-Investigator: Mariee Grima         
Sub-Investigator: David Barton         
Sub-Investigator: Arup Dhar         
Sub-Investigator: Sarah Tremethick         
Sub-Investigator: Nora Straznicky         
Sub-Investigator: John Dixon         
Sub-Investigator: Jennifer Grigo         
Sub-Investigator: Donna Vizi         
Sub-Investigator: Louise Hammond         
Sponsors and Collaborators
Baker IDI Heart and Diabetes Institute
The Alfred
Monash Medical Centre
Ballarat Health Service Psychiatric Services
Investigators
Study Director: Gavin Lambert Baker IDI Heart & Diabetes Institute
Principal Investigator: David Barton Monash Medical Centre
Principal Investigator: Abdul Khalid Ballarat Health Service Psychiatric Services
  More Information

No publications provided

Responsible Party: Baker IDI Heart and Diabetes Institute
ClinicalTrials.gov Identifier: NCT01567124     History of Changes
Other Study ID Numbers: 108/12, 1022794
Study First Received: March 25, 2012
Last Updated: December 16, 2013
Health Authority: Australia: Human Research Ethics Committee
Australia: Department of Health and Ageing Therapeutic Goods Administration
Australia: National Health and Medical Research Council

Keywords provided by Baker IDI Heart and Diabetes Institute:
Schizophrenia
Moxonidine
Sympathetic nervous system activation
Cardiometabolic side effects of antipsychotics

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Antipsychotic Agents
Moxonidine
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Antihypertensive Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on August 21, 2014