Predictors of Antidepressant Response

NCT02178696 | Completed Phase 4 Results

• 1 other identifier: HUM00033328
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

Major depression is a highly prevalent, frequently debilitating illness that too often fails to respond to currently available treatments such as antidepressant medication. Furthermore, randomized controlled trials of antidepressants consistently demonstrate large placebo effects. The investigators hypothesize that individual differences in the function of key brain circuits underlie the observed variability in clinical responses to both placebo and antidepressant medication. This study will test this hypothesis by recruiting treatment-seeking volunteers with major depression, with or without comorbid nicotine dependence. Volunteers will participate in positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) scans in the context of a treatment trial in which they will receive both placebo and antidepressant medication. A major goal of the study is to improve prediction of individual clinical responses in future treatment trials in which brain imaging may be unavailable, and to study the mechanisms of antidepressant response in Major Depression.

Conditions

Depression

Outcome Measures

Primary Outcomes (2)

• Changes in Mu-opioid Binding Potential During PET

  Binding Potential = Bmax/Kd (receptor concentration/affinity). This is the most common measure of in vivo receptor binding with positron emission tomography. Whole brain changes in mu-opioid receptors binding potential during PET from the Inactive to the Active placebo condition. Positive numbers presented here represent reductions in binding potential from the inactive to the active condition.

  (90 minute PET scans) assessed at Weeks 1 and 2

• Changes in BOLD Response During Reward fMRI Task (Monetary Incentive Delay, MID)

  % BOLD signal changes in the nucleus accumbens from the Inactive to the Active Placebo condition.

  (90 minute fMRI scans) assessed at Weeks 1 and 2

Secondary Outcomes (5)

• Changes in Dopamine (D 2/3) Binding Potential During PET.

  (90 minute PET scan) assessed at Weeks 1 and 2

• Changes From Baseline in Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR-16) Score

  From Pre to post- active placebo, and from pre to post- inactive placebo (1 week intervention)

• Changes From Baseline in PHQ-9 Depression Scores.

  From Pre to post- active placebo, and from pre to post- inactive placebo (1 week intervention)

• Hamilton Depression Rating Scale Scores

  Screening, week 0, week 2, week 4, week 8 and week 10

• Montgomery-Asberg Depression Rating Scale

  Screening, week 0, week 2, week 4, week 8 and week 10

Study Arms (2)

Known Placebo First

EXPERIMENTAL

This arm gets a placebo that they know is a placebo (called inactive), then has 2 scans performed (FMRI and PET), then a 2-3 day washout, and then gets a so-called "active medication" (which is also actually a placebo), and another pair of scans. Following these, participants receive 10 weeks of open-label antidepressant administration (Celexa or alternative as explained in intervention description). First line antidepressant will be Celexa unless not clinically indicated.

Other: Placebo, identified as placebo to participants; Drug: Celexa or other antidepressant as clinically indicated; Other: Placebo, identifed to participants as "Active medication"

"Active" (blinded) Placebo first group

EXPERIMENTAL

This arm gets a placebo that they don't know is a placebo (called Active), then has 2 scans performed (FMRI and PET), then a 2-3 day washout, and then gets a so-called "inactive medication" (which participants know is a placebo), and another pair of scans. Following these, participants receive 10 weeks of open-label antidepressant administration (Celexa as explained in intervention description). First line antidepressant will be Celexa unless not clinically indicated.

Other: Placebo, identified as placebo to participants; Drug: Celexa or other antidepressant as clinically indicated; Other: Placebo, identifed to participants as "Active medication"

Interventions

Placebo, identified as placebo to participants OTHER

White tablets

"Active" (blinded) Placebo first group; Known Placebo First

Celexa or other antidepressant as clinically indicated DRUG

Open label s-citalopram, 20 mg start up dose, increasing to 40 mg as clinically indicated; If prior non-response to this medication is noted by the patient, alternative treatments may include another first-line antidepressant:fluoxetine 20 mg; paroxetine up to 60 mg; sertraline up to 200 mg; bupropion up to 300 mg

Also known as: S-citalopram 20-40 mg orally

"Active" (blinded) Placebo first group; Known Placebo First

Placebo, identifed to participants as "Active medication" OTHER

Blue Capsule

"Active" (blinded) Placebo first group; Known Placebo First

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Participants diagnosed with Major Depressive Disorder and will include Hamilton Depressive Rating Scale (HDRS) scores \>15

You may not qualify if:

• Comorbid conditions that are medical, neurological or psychiatric, pregnancy, use of hormones (including birth control) or use of psychotropic agents
• We will only permit certain past anxiety disorder diagnoses, including generalized anxiety, panic, agoraphobia, social phobia
• We also will exclude left-handed individuals and patients who have used any centrally acting medications or recreational drugs with the past 2 months
• No history of an implant, pacemaker or pacemaker wires, open heart surgery, artificial heart valve, brain aneurysm surgery, middle ear implant, hearing aid, braces or extensive dental work, cataract surgery or lens implant, implanted mechanical or electrical device, or artificial limb or joint
• No metallic object in their body (such as braces) or have a history of foreign metallic object in the body such as bullets, BB's, pellets, shrapnel, or other metal fragments

Sponsors & Collaborators

• University of Michigan: lead

Study Sites (1)

Department of Psychiatry

Ann Arbor, Michigan, 48108, United States

Location

Related Publications (2)

• Pecina M, Bohnert AS, Sikora M, Avery ET, Langenecker SA, Mickey BJ, Zubieta JK. Association Between Placebo-Activated Neural Systems and Antidepressant Responses: Neurochemistry of Placebo Effects in Major Depression. JAMA Psychiatry. 2015 Nov;72(11):1087-94. doi: 10.1001/jamapsychiatry.2015.1335.

  PMID: 26421634 RESULT

• Sikora M, Heffernan J, Avery ET, Mickey BJ, Zubieta JK, Pecina M. Salience Network Functional Connectivity Predicts Placebo Effects in Major Depression. Biol Psychiatry Cogn Neurosci Neuroimaging. 2016 Jan;1(1):68-76. doi: 10.1016/j.bpsc.2015.10.002.

  PMID: 26709390 RESULT

MeSH Terms

Conditions

Depression

Interventions

Citalopram; Dexetimide

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Jon-Kar Zubieta
• Organization: University of Michigan

JONKAR.ZUBIETA@hsc.utah.edu

Study Officials

• Jon-Kar Zubieta, MD, PhD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD

Study Record Dates

• First Submitted: June 12, 2014
• First Posted: July 1, 2014
• Study Start: January 1, 2011
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: December 5, 2017
• Results First Posted: December 5, 2017

Record last verified: 2017-10

Locations

US (1)