NCT01567124

Alleviating the Metabolic Side Effects of Antipsychotic Medications

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

• Status: Withdrawn
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Baker Heart and Diabetes Institute · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Schizophrenia

Interventions

Type	Name	Description
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.
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.
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.
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.

Timeline

• Start date: 2012-05-01
• First posted: 2012-03-30
• Last updated: 2019-04-24

Locations

4 sites across 1 country: Australia