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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/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] 0 0
1022794
Secondary ID [2] 0 0
108/12
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Schizophrenia 0 0
Condition category
Condition code
Mental Health 0 0 0 0
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At the end of the twelve weeks of treatment, participants will be withdrawn from moxonidine over a period of two weeks.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] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To determine the association between sympathetic nervous system and metabolic abnormalities (eg, weight gain) observed with antipsychotic treatment.
Timepoint [1] 0 0
Baseline and following 12 weeks of moxonidine/placebo treatment.
Secondary outcome [1] 0 0
Change from baseline in sympathetic nervous system activity.
Timepoint [1] 0 0
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?
No
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
0
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Ballarat Health Service Psychiatric Services - Ballarat
Recruitment hospital [2] 0 0
Monash Medical Centre - Monash Health - Clayton
Recruitment hospital [3] 0 0
Alfred and Baker Medical Unit - Alfred Hospital - Melbourne
Recruitment hospital [4] 0 0
Baker IDI Heart & Diabetes Institute - Melbourne
Recruitment postcode(s) [1] 0 0
- Ballarat
Recruitment postcode(s) [2] 0 0
- Clayton
Recruitment postcode(s) [3] 0 0
- Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Baker Heart and Diabetes Institute
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
The Alfred
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Monash Medical Centre
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Ballarat Health Services
Address [3] 0 0
Country [3] 0 0

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/ct2/show/NCT01567124
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gavin Lambert
Address 0 0
Baker IDI Heart & Diabetes Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01567124