SchizophreniaPhase 4NCT01567124
Alleviating the Metabolic Side Effects of Antipsychotic Medications
A Phase 4 study testing Moxonidine in people with Schizophrenia, run by Baker Heart and Diabetes Institute at 4 sites in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Moxonidine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 4 sitesAustralia
- Study dates
- May 2012to not given
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
4 sites in 1 country.
Australia4 sites
Ballarat Health Service Psychiatric Services
Ballarat, Victoria
Monash Medical Centre - Monash Health
Clayton, Victoria
Alfred and Baker Medical Unit - Alfred Hospital
Melbourne, Victoria
Baker IDI Heart & Diabetes Institute
Melbourne, Victoria
About this study
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
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.
Read more
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.
- Conditions
- Schizophrenia
- Being tested
- Moxonidine, Placebo
- Keywords
- Schizophrenia, Moxonidine, Sympathetic nervous system activation, Cardiometabolic side effects of antipsychotics
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MoxonidineDrug
Also called Physiotens
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.
PlaceboDrug
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.
MoxonidineDrug
Also called Physiotens
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Olanzapine | Other | Participants taking olanzapine at the time of recruitment will continue to take this medication as part of standard care for schizophrenia. Receives: Drug: Moxonidine; Drug: Placebo |
| Clozapine | Other | Participants taking clozapine at the time of recruitment will continue to take this medication as part of standard care for schizophrenia. Receives: Drug: Moxonidine; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the association between sympathetic nervous system and metabolic abnormalities (eg, weight gain) observed with antipsychotic treatment.
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.
Measured: Baseline and following 12 weeks of moxonidine/placebo treatment.
Secondary outcomes (1)
Change from baseline in sympathetic nervous system activity.
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.
Measured: Baseline and following 12 weeks of moxonidine/placebo treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2012 (estimated)
- Study startMay 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baker Heart and Diabetes Institute
- Sponsor type
- University, hospital or other
- Collaborators
- The Alfred, Monash Medical Centre, Ballarat Health Services
- Responsible party
- Sponsor
- Investigators
- Gavin Lambert, Study director, Baker IDI Heart & Diabetes InstituteDavid Barton, Principal investigator, Monash Medical CentreAbdul Khalid, Principal investigator, Ballarat Health Services
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01567124
- Sponsor's protocol ID
- 108/12
- Other IDs
- 1022794
- Status last verified
- Apr 2019
- First submitted
- 25 Mar 2012
- Last updated
- 24 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01567124
- Acronym / sponsor ID
- 108/12
- Conditions
- Schizophrenia
- Keywords
- Schizophrenia, Moxonidine, Sympathetic nervous system activation, Cardiometabolic side effects of antipsychotics
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Baker Heart and Diabetes InstituteUniversity, hospital or other
- Collaborators
- The Alfred, Monash Medical Centre, Ballarat Health Services
- Study start
- May 2012
- First posted
- 30 Mar 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Olanzapine | Other | Drug: Moxonidine, Drug: PlaceboParticipants taking olanzapine at the time of recruitment will continue to take this medication as part of standard care for schizophrenia. |
| Clozapine | Other | Drug: Moxonidine, Drug: PlaceboParticipants taking clozapine at the time of recruitment will continue to take this medication as part of standard care for schizophrenia. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MoxonidineAlso: PhysiotensParticipants 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. | Drug | Olanzapine |
| PlaceboTo 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. | Drug | Olanzapine |
| MoxonidineAlso: PhysiotensParticipants 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. | Drug | Clozapine |
| PlaceboTo 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. | Drug | Clozapine |
Primary outcome
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.
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.
1 secondary outcome
Change from baseline in sympathetic nervous system activity.
Time frame: Baseline and following 12 weeks of moxonidine/placebo treatment.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gavin Lambert study director
Baker IDI Heart & Diabetes Institute
David Barton principal investigator
Monash Medical Centre
Abdul Khalid principal investigator
Ballarat Health Services
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Moxonidine in people with Schizophrenia, run by Baker Heart and Diabetes Institute at 4 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 24 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2019.