A Multi-level Life-span Characterization of Adult-depression and Effects of Medication and Exercise

NCT02407704 | Completed Phase 4 Results

• 3 other identifiers: MH090333-04PRO13110090MH090333
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot study aims to test a model that predicts that enhanced neurotransmitter gamma-aminobutyric acid (GABA) function in reward and affect-regulation central nervous system (CNS) circuits mediates the antidepressant effects of exercise. State-of-the-art magnetic resonance (MR) imaging, cognitive assessment, accelerometry, genetic, and inflammatory biomarkers will be acquired through the coordination of efforts from several established research programs at Western Psychiatric Institute and Clinic. This pilot study will be used as a platform for testing a causal/mediating role of GABA interneurons in reward processing and affect regulation in humans. This pilot study is not powered for testing a full causal model, but rather is intended to test overall feasibility of the intervention and acquisition of measures (see specific aim 1 below). This is a necessary prerequisite for designing a larger more definitive study of the model, which will be a component of a future grant application. Additionally, the data from this study will be used to test the clinical efficacy of exercise as an adjunctive treatment for late life depression (LLD; Specific Aim 2), as well as imaging, cognitive, and sleep aims (Specific Aims 3 and 4).

Conditions

Depression; Depressive Disorder, Major; Depressive Disorder; Unipolar Depression; Major Depressive Disorder

Keywords

Exercise; Physical activity; GABA; Venlafaxine; fMRI; Spectroscopy; Reward system; BDNF; Sleep; Cognitive function; Biomarkers; Aerobic exercise

Outcome Measures

Primary Outcomes (1)

• Number of Participants Experiencing Remission

  Study completers will be classified as remitters vs. non-remitters. Remission will be defined as a MADRS score of 10 or less for at least two consecutive assessments. The MADRS will also be used to assess clinical response throughout the trial and to determine final medication dosage. At the end of week 6, those with a MADRS score greater than 10 will have the venlafaxine XR increased from 150 mg/d to a maximum of 300 mg/d.

  Baseline, weekly for weeks 1 and 2, then biweekly for weeks 4-12

Secondary Outcomes (6)

• Inflammatory Biomarkers

  Baseline and 12 weeks

• Genetic Biomarkers

  Baseline and 12 weeks

• Physical Activity (SenseWear Physical Activity-monitoring Armband)

  Baseline and 12 weeks

• Cardiovascular Fitness (Submaximal VO2)

  Baseline and 12 weeks

• Functional Magnetic Resonance Imaging (fMRI)

  Baseline and 12 weeks

Study Arms (2)

Aerobic Exercise + Venlafaxine XR

EXPERIMENTAL

Venlafaxine (Effexor) Extended-Release (XR) comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Exercise will include walking on a treadmill 1 hour 3 times/week for 12 weeks. Heart rate will be closely monitored during sessions. The intensity of the exercise will start at 50% of the age-based maximum for the first week and then increase and be maintained at 60-70% of the age-based maximum for the remainder of the intervention. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours).

Drug: Venlafaxine XR; Other: Aerobic Exercise; Drug: Lorazepam

Venlafaxine XR Only

ACTIVE COMPARATOR

Venlafaxine (Effexor) XR comes in capsule form and is taken by mouth. Target dose will be 150mg/d, with a maximum dose of 300mg/d (response dependent) for a minimum of 12 weeks. Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. This will be administered in pill form (2mg or less per 24 hours).

Drug: Venlafaxine XR; Drug: Lorazepam

Interventions

Venlafaxine XR DRUG

Also known as: Effexor XR

Aerobic Exercise + Venlafaxine XR; Venlafaxine XR Only

Aerobic Exercise OTHER

Also known as: Physical Activity, Cardiovascular Exercise

Aerobic Exercise + Venlafaxine XR

Lorazepam DRUG

Lorazepam may be used in the study for patients who either are already on this drug or who need it for sleep and/or anxiety. Patients taking another benzodiazepine will be asked to convert from their current benzodiazepine to an equivalent dose of Lorazepam (2mg or less in 24 hours). This will be administered in pill form.

Also known as: Ativan

Aerobic Exercise + Venlafaxine XR; Venlafaxine XR Only

Eligibility Criteria

• Age: 60 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages 20-39 (recruitment complete) and 60-79 years old (open to recruitment)
• Major depressive disorder (MDD), single or recurrent, as diagnosed by the PRIME-MD
• MADRS ≥ 15
• In-town and available to commute to Oakland for a 12-week period
• Study nurse practitioner approval to participate in a 12-week moderate intense exercise intervention
• Eligible to undergo MRI

You may not qualify if:

• Inability to provide informed consent.
• Modified Mini-Mental Score (3MS) less than 84 or dementia based upon Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria including poor performance on the clinical neuropsychological battery, IQCODE, and all available clinical information.
• Lifetime diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms.
• Abuse of or dependence on alcohol or other substances within the past three months
• High risk for suicide \[e.g., active suicidal ideation (SI) and/or current/recent intent or plan\] AND unable to be managed safely in the clinical trial (e.g., unwilling to be hospitalized). Urgent psychiatric referral will be made in these cases.
• Contraindication to venlafaxine XR as determined by study physician including history of intolerance of venlafaxine XR in the study target dosage range (venlafaxine XR at up to 300 mg/day).
• Inability to communicate in English (i.e., interview cannot be conducted without an interpreter; subject largely unable to understand questions and cannot respond in English).
• Non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview)
• Unstable/uncontrolled medical illness, including delirium, hypertension, hyperlipidemia, or cerebrovascular or cardiovascular risk factors that are not under medical management.
• Subjects taking psychotropic medications that cannot be safely tapered or discontinued prior to study initiation
• If a patient failed a trial of venlafaxine (12 weeks of treatment with venlafaxine including at least 6 weeks on 300mg/day), he/she would not be eligible.
• Other drugs that may affect the GABA system will be excluded (e.g., Kava, Valerian, Theanine, and GABA supplements).
• The drug Linezolid (Zyvox) should be discontinued prior to study enrollment and should not be used during the study.
• Current medical condition or treatment for a medical condition that could affect balance, gait, or contraindicate participation in moderate intensity physical activity.
• Observed gait condition or use of walking assisted device that would contraindicate use of treadmill for exercise testing and intervention.

Sponsors & Collaborators

• Kirk Erickson, PhD: lead

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (25)

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MeSH Terms

Conditions

Depression; Depressive Disorder, Major; Depressive Disorder; Motor Activity

Interventions

Venlafaxine Hydrochloride; Exercise; Lorazepam

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Organic Chemicals; Phenethylamines; Ethylamines; Amines; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Lipids; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Kirk Erickson
• Organization: University of Pittsburgh

kiericks@pitt.edu

412-624-4533

Study Officials

• Kirk Erickson, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor/Principal Investigator

Study Record Dates

• First Submitted: March 25, 2015
• First Posted: April 3, 2015
• Study Start: March 1, 2015
• Primary Completion: November 1, 2016
• Study Completion: December 1, 2016
• Last Updated: May 23, 2018
• Results First Posted: May 23, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)