DepressionPhase 4MEDEXNCT02407704

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

A Phase 4 study testing Venlafaxine XR, Aerobic Exercise and Lorazepam in people with Depression and Depressive Disorder, Major, run by Kirk Erickson, PhD at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 60 to 79 years
Conditions the study is for: Depression, Depressive Disorder, Major, Depressive Disorder
What is being tested?: Venlafaxine XR, Aerobic Exercise and Lorazepam
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 31 participants
Where: 1 siteUnited States
Study dates: Mar 2015to Dec 2016
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 60 to 79 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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).

Show all 20Show fewer

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.
Exclusion criteria for MR scans include: cardiac pacemaker, aneurysm clip, cochlear implant, pregnancy, intrauterine device, shrapnel, history of metal fragments in the eye, neurostimulators, weight >250 lbs., tinnitus, or claustrophobia.
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.
Current congestive heart failure, angina, uncontrolled arrhythmia, or other symptoms indicative of an increased acute risk for a cardiovascular event; within the previous 12 months having a myocardial infarction, coronary artery bypass grafting, or angioplasty; conditions requiring chronic anticoagulation (i.e. recent or recurrent DVT).
Eating disorders that would contraindicate physical activity.
Report exercise on more than three days per week for greater than 20 minutes per day over the past three months.
Report plans to relocate to a location not accessible to the study site or having employment, personal, or travel commitments that prohibit attendance to at least 80 percent of the scheduled intervention sessions and all of the scheduled assessments.

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Pittsburgh
Pittsburgh, Pennsylvania, 15213

Other trials in United States

About this study

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).

Read the detailed description

Specific Aims:

Aim 1: Establish the infrastructure, protocol, and procedures for recruiting, screening, enrolling, and maintaining a sample of 30 adults (both younger adults and older adults) with major depression in a 12-week exercise intervention. The primary aim is to establish both feasibility and proof-of-concept on a wide range of biologically and clinically relevant outcomes.

Aim 2: Examine whether the 12-week physical activity + pharmacotherapy intervention reduces depressive symptoms in both younger and older adults above and beyond that of treatment as usual (TAU). Hypothesis 1: In both younger and older adults the antidepressant properties of pharmacotherapy will be augmented when combined with aerobic exercise such that the combined intervention will have higher rates of response and remission compared to only pharmacotherapy treatment.

Aim 3: Examine whether the 12-week combined physical activity and pharmacotherapy intervention changes the structural morphology in specific subfields of the hippocampus. Hypothesis 1: The medication intervention will increase hippocampal volume in the dentate gyrus and carbonic anhydrase I (CA1), but combining aerobic exercise with pharmacotherapy will magnify the effects of exercise. Hypothesis 2: The effect on hippocampal volume will be larger for older versus younger adults Aim 4: Explore how the combination of pharmacotherapy and exercise (compared with pharmacotherapy and TAU) influences a range of brain and behavioral outcomes, including resting state brain dynamics, MR spectroscopic measures of GABA, sleep efficiency, and cognitive performance. Hypothesis 1: Antidepressant pharmacotherapy will alter resting state networks, increase GABA levels, and improve sleep efficiency and cognitive performance - but these effects will be greater when combined with an aerobic exercise intervention. Hypothesis 2: These effects will be moderated by age such that the effects will be greater in older adults, supporting a dissociation between depression in younger and adults, and providing justification for fully powered study to explore these models and treatment-predictive biomarkers.

Depression is a significant global public health concern; it is the second leading cause of disability worldwide and is currently estimated to affect 350 million people. Antidepressant medications have shown to be more effective than placebo in treating depression. However, for 20-40% of individuals suffering from depression the pharmacotherapy has a slow or inadequate response. Thus, identifying alternative treatments for depression is a public health priority.

Background:

Physical activity is emerging as one of the most promising non-pharmaceutical treatments for depression. Greater amounts of self-reported physical activity are associated with fewer depressive symptoms in epidemiological studies and randomized interventions find that participation in physical activity enhances mood in depressed populations. A Cochrane review of 32 randomized interventions concluded that participation in physical activity is effective for reducing depressive symptoms compared to either no treatment or to a control condition. Importantly, antidepressants and physical activity may work through similar biological pathways to influence both mood and cognitive function. In fact, both antidepressants and physical activity increase levels of Brain-derived neurotrophic factor (BDNF) in serum and hippocampus, may mitigate or reverse hippocampal atrophy, influence expression and kinetics of serotonin and GABA pathways, regulate brain network connectivity, alter inflammatory pathways, and improve sleep efficiency. Our proposal aims to characterize these effects from the genetic to the behavioral and cognitive level, and isolate the effects of physical activity from those of medication.

Significance:

If effective, physical activity could become a first line of treatment for depression, which might also help reduce cognitive deficits, job productivity, and risk of other psychiatric conditions. Furthermore, although physical exercise has shown promise in reducing depressive symptoms, researchers still do not understand the biological pathways by which it works. One of the leading hypotheses of depression is that disruptions in GABA systems underlies the deficits. In contrast, improvements in GABA signaling is one of the ways in which exercise may improve brain function and reduce depressive symptoms. Along this line, investigators hope to determine the type of exercise (aerobic versus stretching and toning) that can be promoted in the future to improve brain function and reduce depressive symptoms. Demonstrating these links could be an important first step for developing more effective treatment plans for those suffering from depression.

Conditions: Depression, Depressive Disorder, Major, Depressive Disorder, Unipolar Depression, Major Depressive Disorder
Being tested: Venlafaxine XR, Aerobic Exercise, Lorazepam
Keywords: Exercise, Physical activity, GABA, Venlafaxine, fMRI, Spectroscopy, Reward system, BDNF, Sleep, Cognitive function, Biomarkers, Aerobic exercise
Medical subject headings: Depression, Depressive Disorder, Major, Depressive Disorder, Motor Activity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Venlafaxine XRDrug
Also called Effexor XR
Aerobic ExerciseOther
Also called Physical Activity, Cardiovascular Exercise
LorazepamDrug
Also called Ativan
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.

Study groups in NCT02407704
Study group	Role	What they receive
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). Receives: 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). Receives: Drug: Venlafaxine XR; Drug: Lorazepam

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (6)

Inflammatory Biomarkers
Blood samples were collected to assess biomarkers, but funding is not yet available to perform analyses.
Measured: Baseline and 12 weeks
Genetic Biomarkers
Blood samples were collected to assess biomarkers, but funding is not yet available to perform analyses.
Measured: Baseline and 12 weeks
Physical Activity (SenseWear Physical Activity-monitoring Armband)
This will be used to acquire objective information about physical activity. This armband is worn around the upper arm (left triceps) for 1 week and collects information about skin temperature, galvanic skin response, heat flux, and motion via a 3-axis accelerometer. This information is used in an algorithm to determine energy expenditure (EE). The device has a resolution of 1-minute indicating that we can acquire the above information on a minute-by-minute basis, which will allow us to determine both duration and intensity of activity during a normal week. Higher values indicate higher levels of activity.
Measured: Baseline and 12 weeks
Cardiovascular Fitness (Submaximal VO2)
Cardiorespiratory fitness was measured via submaximal VO2 on a motorized treadmill while measuring oxygen utilization via Parvo Medics True one metabolic cart. The submaximal test followed a modified Balke protocol in which speed remained constant with the intensity being increased every two minutes via a raise of 2.0% of the incline. The speed was an agreed upon speed between participant and staff (between 2.0 and 4.0 mph). The submaximal VO2 was stopped when participant reached 85% of age predicted maximal heart rate (220 - age), rating of perceived exertion (RPE) equal to or greater than 15 for those who have blunted heart rate response due to beta block medication, or volitional termination by participant. Vital signs were monitored throughout the test and cool down period. Peak VO2 values for this cohort ranged from 14.04 to 36.48 ml/kg/min, with higher values correlated to higher fitness level.
Measured: Baseline and 12 weeks
Functional Magnetic Resonance Imaging (fMRI)
Brain imaging conducted with a 7 Tesla scanner. Of particular interest were changes in hippocampal volume, GABA, and glutamate. The changes regarding hippocampal volumes are reported below. This measurement is reported in mm^3, with higher numbers indicating higher levels of gray matter in the hippocampal region. Volume is combined between right and left hemispheres. GABA and glutamate are not reported. The method used to obtain the data was being piloted for this study, and due to methodological challenges, the data is not considered to be accurate and therefore cannot be analyzed/shared.
Measured: Baseline and 12 weeks
Neurocognitive Function (Neuropsychological Battery)
The battery evaluates several cognitive domains. The Wechsler Adult Intelligence Scale, 4th ed. Digit Span subtest assesses attention and working memory. The Repeatable Battery of Neuropsychological Status (RBANS) measures Immediate and Delayed Memory, Attention, Language Abilities, and Visuospatial Functioning. Total index scores range from 40-155. The California Verbal Learning Test, 2nd Ed. (CVLT) assesses non-contextual verbal learning and memory. Z-scores are calculated for each of the constructs assessed by the CVLT. Subtests from the Deli-Kaplan Executive Function System (D-KEFS) assess aspects of executive functioning, including set-shifting (Trail Making Test Conditions 4 and 5: scaled score ranging from 0-19) and inhibition (Color-Word Interference Test Condition 3: weighted scaled score ranging from 1-19). Given that standardized scores are calculated for each of the neuropsychological measures, higher scores always indicate better cognitive functioning.
Measured: Baseline and 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2015Dec 2016

First posted3 Apr 2015 (estimated)
Study startMar 2015
Primary completionNov 2016
Study completionDec 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (25)Papers the sponsor has linked to this study.
Other trials for DepressionStudies 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: None (open label)
Enrolment: 31 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02407704
Sponsor's protocol ID: MH090333-04
Other IDs: PRO13110090, MH090333
Acronym: MEDEX
Status last verified: Apr 2018
First submitted: 25 Mar 2015
Last updated: 23 May 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No

Publications

Butters MA, Young JB, Lopez O, Aizenstein HJ, Mulsant BH, Reynolds CF 3rd, DeKosky ST, Becker JT. Pathways linking late-life depression to persistent cognitive impairment and dementia. Dialogues Clin Neurosci. 2008;10(3):345-57. doi: 10.31887/DCNS.2008.10.3/mabutters.
PubMed 18979948
Kohler S, Thomas AJ, Barnett NA, O'Brien JT. The pattern and course of cognitive impairment in late-life depression. Psychol Med. 2010 Apr;40(4):591-602. doi: 10.1017/S0033291709990833. Epub 2009 Aug 6.
PubMed 19656429
Tedeschini E, Levkovitz Y, Iovieno N, Ameral VE, Nelson JC, Papakostas GI. Efficacy of antidepressants for late-life depression: a meta-analysis and meta-regression of placebo-controlled randomized trials. J Clin Psychiatry. 2011 Dec;72(12):1660-8. doi: 10.4088/JCP.10r06531.
PubMed 22244025
Galper DI, Trivedi MH, Barlow CE, Dunn AL, Kampert JB. Inverse association between physical inactivity and mental health in men and women. Med Sci Sports Exerc. 2006 Jan;38(1):173-8. doi: 10.1249/01.mss.0000180883.32116.28.
PubMed 16394971
Hassmen P, Koivula N, Uutela A. Physical exercise and psychological well-being: a population study in Finland. Prev Med. 2000 Jan;30(1):17-25. doi: 10.1006/pmed.1999.0597.
PubMed 10642456
Barbour KA, Edenfield TM, Blumenthal JA. Exercise as a treatment for depression and other psychiatric disorders: a review. J Cardiopulm Rehabil Prev. 2007 Nov-Dec;27(6):359-67. doi: 10.1097/01.HCR.0000300262.69645.95.
PubMed 18197069
Rimer J, Dwan K, Lawlor DA, Greig CA, McMurdo M, Morley W, Mead GE. Exercise for depression. Cochrane Database Syst Rev. 2012 Jul 11;(7):CD004366. doi: 10.1002/14651858.CD004366.pub5.
PubMed 22786489
Blumenthal JA, Babyak MA, Doraiswamy PM, Watkins L, Hoffman BM, Barbour KA, Herman S, Craighead WE, Brosse AL, Waugh R, Hinderliter A, Sherwood A. Exercise and pharmacotherapy in the treatment of major depressive disorder. Psychosom Med. 2007 Sep-Oct;69(7):587-96. doi: 10.1097/PSY.0b013e318148c19a. Epub 2007 Sep 10.
PubMed 17846259
Erickson KI, Miller DL, Roecklein KA. The aging hippocampus: interactions between exercise, depression, and BDNF. Neuroscientist. 2012 Feb;18(1):82-97. doi: 10.1177/1073858410397054. Epub 2011 Apr 29.
PubMed 21531985
Garza AA, Ha TG, Garcia C, Chen MJ, Russo-Neustadt AA. Exercise, antidepressant treatment, and BDNF mRNA expression in the aging brain. Pharmacol Biochem Behav. 2004 Feb;77(2):209-20. doi: 10.1016/j.pbb.2003.10.020.
PubMed 14751447
Blumenthal JA, Babyak MA, Moore KA, Craighead WE, Herman S, Khatri P, Waugh R, Napolitano MA, Forman LM, Appelbaum M, Doraiswamy PM, Krishnan KR. Effects of exercise training on older patients with major depression. Arch Intern Med. 1999 Oct 25;159(19):2349-56. doi: 10.1001/archinte.159.19.2349.
PubMed 10547175
Mather AS, Rodriguez C, Guthrie MF, McHarg AM, Reid IC, McMurdo ME. Effects of exercise on depressive symptoms in older adults with poorly responsive depressive disorder: randomised controlled trial. Br J Psychiatry. 2002 May;180:411-5. doi: 10.1192/bjp.180.5.411.
PubMed 11983637
Organization WH: Depression: A global public health concern, WHO Department of Mental Health and Substance Abuse,
Steenland K, Karnes C, Seals R, Carnevale C, Hermida A, Levey A. Late-life depression as a risk factor for mild cognitive impairment or Alzheimer's disease in 30 US Alzheimer's disease centers. J Alzheimers Dis. 2012;31(2):265-75. doi: 10.3233/JAD-2012-111922.
PubMed 22543846
Reynolds SL, Haley WE, Kozlenko N. The impact of depressive symptoms and chronic diseases on active life expectancy in older Americans. Am J Geriatr Psychiatry. 2008 May;16(5):425-32. doi: 10.1097/JGP.0b013e31816ff32e.
PubMed 18448853

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 23 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multi-level Life-span Characterization of Adult-depression and Effects of Medication and Exercise
ClinicalTrials.gov ID: NCT02407704
Acronym / sponsor ID: MEDEX / MH090333-04
Conditions: Depression, Depressive Disorder, Major, Depressive Disorder, Unipolar Depression, Major Depressive Disorder
Keywords: Exercise, Physical activity, GABA, Venlafaxine, fMRI, Spectroscopy, Reward system, BDNF
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 31 participants (actual)
Lead sponsor: Kirk Erickson, PhDUniversity, hospital or other
Study start: Mar 2015
Primary completion: Nov 2016 (actual)
Study completion: Dec 2016 (actual)
First posted: 3 Apr 2015 (estimated)
Results: Posted 23 May 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Specific Aims:

Background:

Significance:

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Aerobic Exercise + Venlafaxine XR	Experimental	Drug: Venlafaxine XR, Other: Aerobic Exercise, Drug: LorazepamVenlafaxine (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).
Venlafaxine XR Only	Active comparator	Drug: Venlafaxine XR, Drug: LorazepamVenlafaxine (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).

Who may qualify

Ages: 60 to 79 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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

Key exclusion criteria (20 listed)

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.

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
Venlafaxine XRAlso: Effexor XR	Drug	Aerobic Exercise + Venlafaxine XR, Venlafaxine XR Only
Aerobic ExerciseAlso: Physical Activity, Cardiovascular Exercise	Other	Aerobic Exercise + Venlafaxine XR
LorazepamAlso: AtivanLorazepam 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.	Drug	Aerobic Exercise + Venlafaxine XR, Venlafaxine XR Only

Primary outcome

Number of Participants Experiencing Remission
Time frame: Baseline, weekly for weeks 1 and 2, then biweekly for weeks 4-12
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.

6 secondary outcomes

Inflammatory Biomarkers
Time frame: Baseline and 12 weeks
Genetic Biomarkers
Time frame: Baseline and 12 weeks
Physical Activity (SenseWear Physical Activity-monitoring Armband)
Time frame: Baseline and 12 weeks
Cardiovascular Fitness (Submaximal VO2)
Time frame: Baseline and 12 weeks
Functional Magnetic Resonance Imaging (fMRI)
Time frame: Baseline and 12 weeks
Neurocognitive Function (Neuropsychological Battery)
Time frame: Baseline and 12 weeks

Results and safety

Results posted to the registry on 23 May 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Aerobic Exercise + Venlafaxine XR (60-79 Years of Age)	2	2
Venlafaxine XR Only (60-79 Years of Age)	3	3
Aerobic Exercise + Venlafaxine XR (20-39 Years of Age)	5	4
Venlafaxine XR Only (20-39 Years of Age)	5	2

Primary outcome: Number of Participants Experiencing Remission

Time frame: Baseline, weekly for weeks 1 and 2, then biweekly for weeks 4-12. Count of participants. Unit: Participants

Measure	Aerobic Exercise + Venlafaxine XR (60-79 Years of Age) n = 2	Venlafaxine XR Only (60-79 Years of Age) n = 3	Aerobic Exercise + Venlafaxine XR (20-39 Years of Age) n = 4	Venlafaxine XR Only (20-39 Years of Age) n = 2
Value	0	2	4	2

Population analysed: 1 participant in the "Venlafaxine XR Only (20-39 Years of Age)" group was excluded from analyses as he/she discontinued the medication after week 8.

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: 12 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Aerobic Exercise + Venlafaxine XR (60-79 Years of Age)	0 of 2 (0%)	1 of 2 (50%)	0 of 2
Venlafaxine XR Only (60-79 Years of Age)	0 of 3 (0%)	3 of 3 (100%)	0 of 3
Aerobic Exercise + Venlafaxine XR (20-39 Years of Age)	0 of 4 (0%)	4 of 4 (100%)	0 of 4
Venlafaxine XR Only (20-39 Years of Age)	0 of 4 (0%)	4 of 4 (100%)	0 of 3

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 18979948Butters MA, Young JB, Lopez O, Aizenstein HJ, Mulsant BH, Reynolds CF 3rd, DeKosky ST, Becker JT. Pathways linking late-life depression to persistent cognitive impairment and dementia. Dialogues Clin Neurosci. 2008;10(3):345-57. doi: 10.31887/DCNS.2008.10.3/mabutters.
Background: PubMed 19656429Kohler S, Thomas AJ, Barnett NA, O'Brien JT. The pattern and course of cognitive impairment in late-life depression. Psychol Med. 2010 Apr;40(4):591-602. doi: 10.1017/S0033291709990833. Epub 2009 Aug 6.
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Brain Aging \& Cognitive Health Lab, University of PittsburghLink provided by the sponsor.
Individual participant dataSharing planned: No

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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.

Kirk Erickson, PhD principal investigator

University of Pittsburgh

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Venlafaxine XR, Aerobic Exercise and Lorazepam in people with Depression and Depressive Disorder, Major, run by Kirk Erickson, PhD at 1 site in United States.

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 6 inclusion and 20 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: finished, as of the sponsor's last update on 23 May 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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?

Yes. Results are posted in the registry (first posted 23 May 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants Experiencing Remission (time frame: Baseline, weekly for weeks 1 and 2, then biweekly for weeks 4-12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02407704, which also lists 25 linked publications.

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 23 May 2018.