A New Treatment Approach for Major Depressive Disorder Based Upon Targeting Monoamine Oxidase A (MAO-A)

A New Biomarker-Based Approach Towards Developing Improved Treatment for Major Depressive Disorder (MDD) Based Upon Targeting Monoamine Oxidase A (MAO-A)

The investigators will be looking at MAO-A density before and after seven weeks of treatment with an antidepressant and dietary supplement. MAO-A is an enzyme that breaks down brain chemicals that regulate mood. MAO-A density is elevated in patients with major depressive episodes (MDE) secondary to major depressive disorder (MDD). Many remain treatment resistant with common antidepressant treatments and we think it may be due to poor targeting of brain pathologies. We want to test if adding a dietary supplement may normalize MAO-A.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Sertraline; Drug: N-acetylcysteine (NAC); Drug: Citalopram; Drug: Existing depression medication treatment

Detailed Description

All subjects are getting the combined treatment of a selective serotonin reuptake inhibitor and the dietary supplement. There are two possible selective serotonin reuptake inhibitor treatments but the dietary supplement remains the same. No subjects are receiving the selective serotonin reuptake inhibitor alone and no subjects are receiving the dietary supplement alone. The dietary supplement is called n-acetylcysteine.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T 1R8
      • Research Imaging Centre, Centre for Addiction and Mental Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• DSM-IV diagnosis of current major depressive episode and major depressive disorder
• Hamilton Depression Rating Scale score of at least 20

Exclusion Criteria:

• Comorbid axis I or II disorders
• Antidepressant use in past 6 months
• Current use of herbal remedies
• Cigarette smoking
• Drug or medication use within past 8 weeks
• History of substance abuse/neurotoxin use
• History of psychotic symptoms
• History of CNS medical illness
• Current substance use
• Test positive on pregnancy test (women)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sertraline and n-acetylcysteine; Sertraline and n-acetylcysteine for seven weeks of treatment	Drug: Sertraline; selective serotonin reuptake inhibitor; Other Names: Zoloft; Drug: N-acetylcysteine (NAC); natural health product
Experimental: Citalopram and n-acetylcysteine; Citalopram and n-acetylcysteine for seven weeks of treatment	Drug: N-acetylcysteine (NAC); natural health product; Drug: Citalopram; selective serotonin reuptake inhibitor; Other Names: Celexa
Experimental: Existing medication treatment & NAC; Existing depression medication treatment and n-acetylcysteine for seven weeks of treatment	Drug: N-acetylcysteine (NAC); natural health product; Drug: Existing depression medication treatment; Continuation of depression medication treatment already taken prior to study enrollment except for drugs with affinity for MAO-A or potentially influencing MAO-A levels, including phenelzine, tranylcypromine, moclobemide, cytomel and lithium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MAO-A distribution volume with positron emission tomography	Treatment take 1 week for titration and 6 weeks at full dose=7weeks average	before and after treatment, 7 weeks on average between measures

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hamilton Depression Rating Scale Score	Treatment takes 1 week for titration and 6 weeks at full dose=7 weeks average	before and after treatment, 7 weeks on average between measures
Magnetic Resonance Spectroscopy (n-acetylaspartate and glutathione levels)	Treatment takes 1 week for titration and 6 weeks at full dose=7 weeks average	before and after treatment, 7 weeks on average between measures
Blood markers of monoamine oxidase-A fragment level and glutathione level	Treatment takes 1 week for titration and 6 weeks at full dose=7 weeks average	before and after treatment, 7 weeks on average between measures

Collaborators and Investigators

• Sponsor: Centre for Addiction and Mental Health
• Investigators: Principal Investigator: Jeffrey H Meyer, MD, PhD, Centre for Addiction and Mental Health; University of Toronto

Publications and helpful links

Helpful Links

• The Centre for Addiction and Mental Health (CAMH) is the leading mental health and addictions research facility in Canada, and one of the largest in the world.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): July 1, 2018

Study Registration Dates

• First Submitted: August 11, 2014
• First Submitted That Met QC Criteria: October 20, 2014
• First Posted (Estimate): October 21, 2014

Study Record Updates

• Last Update Posted (Actual): May 24, 2019
• Last Update Submitted That Met QC Criteria: May 22, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Sertraline; Citalopram; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: 137/2013