- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02178696
Predictors of Antidepressant Response
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Michigan
-
Ann Arbor, Michigan, United States, 48108
- Department of Psychiatry
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria: Inclusion criteria will include:
- Participants diagnosed with Major Depressive Disorder and will include Hamilton Depressive Rating Scale (HDRS) scores >15
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Known Placebo First
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.
|
White tablets
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
Other Names:
Blue Capsule
|
Experimental: "Active" (blinded) Placebo first group
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.
|
White tablets
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
Other Names:
Blue Capsule
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in Mu-opioid Binding Potential During PET
Time Frame: (90 minute PET scans) assessed at Weeks 1 and 2
|
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)
Time Frame: (90 minute fMRI scans) assessed at Weeks 1 and 2
|
% 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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in Dopamine (D 2/3) Binding Potential During PET.
Time Frame: (90 minute PET scan) assessed at Weeks 1 and 2
|
Binding Potential= Bmax/Kd (receptor concentration/affinity). This is the most common measure of in vivo receptor binding with PET. Striatal changes in D2/3 receptor binding potential during PET from the Inactive to the Active condition. Positive numbers presented here represented reductions in binding potential from the inactive to the active condition. |
(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
Time Frame: From Pre to post- active placebo, and from pre to post- inactive placebo (1 week intervention)
|
This scale is a self-report measure of depression with 16 items. Questions in the QIDS - SR-116 correlate with the nine DSM-IV symptom criterion domains, Including: Sleep disturbance (initial, middle, and late insomnia or hypersomnia) (Q 1 - 4), Sad mood (Q 5), Decrease/increase in appetite/weight (Q 6 - 9), Concentration (Q 10), Self-criticism (Q 11), Suicidal ideation (Q 12), Interest (Q 13), Energy/fatigue (Q 14), Psychomotor agitation/retardation (Q 15 - 16). Severity of depression can be judged based on the total score: 1-5= No depression; 6-10= Mild depression; 11-15= Moderate depression; 16-20= Severe depression; 21-27= Very severe depression. The PHQ-9 and QIDS were used to assess changes in mood during the placebo intervention (first 2 weeks), and therefore results are described as changes from the inactive to the active condition. |
From Pre to post- active placebo, and from pre to post- inactive placebo (1 week intervention)
|
Changes From Baseline in PHQ-9 Depression Scores.
Time Frame: From Pre to post- active placebo, and from pre to post- inactive placebo (1 week intervention)
|
The Patient Health Questionnaire-9, is a multipurpose instrument for screening, diagnosing, monitoring and measuring the severity of depression, based on participant answers. PHQ-9 scores of 5, 10, 15, and 20 represents mild, moderate, moderately severe and severe depression, respectively. The minimum possible score is 0 and the maximum possible score is 27. The PHQ-9 and QIDS were used to assess changes in mood during the placebo intervention (first 2 weeks), and therefore results are described as changes from the inactive to the active condition. |
From Pre to post- active placebo, and from pre to post- inactive placebo (1 week intervention)
|
Hamilton Depression Rating Scale Scores
Time Frame: Screening, week 0, week 2, week 4, week 8 and week 10
|
The total score is obtained by summing the score of each item, 0-4 (symptom is absent, mild, moderate, or severe) or 0-2 (absent, slight or trivial, clearly present). For the 17-item version, scores can range from 0 to 54, with 0 meaning no depression, and 54, severe depression. The Hamilton Depression Rating Scale was used to assess symptoms during the open label antidepressant treatment phase, so results are described as mean scores at each bi-weekly visit. |
Screening, week 0, week 2, week 4, week 8 and week 10
|
Montgomery-Asberg Depression Rating Scale
Time Frame: Screening, week 0, week 2, week 4, week 8 and week 10
|
Designed in 1979 by researchers as an adjunct to the Hamilton Rating Scale for Depression (HAMD) which would be more sensitive to the changes brought on by antidepressants and other forms of treatment than the Hamilton Scale. MADRS was used to assess symptoms during the open label antidepressant treatment phase, so results are described as mean scores at each bi-weekly visit. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60 where 0 is no depression and 60 is most extreme depression. The questionnaire includes questions on the following symptoms 1. Apparent sadness 2. Reported sadness 3. Inner tension 4. Reduced sleep 5. Reduced appetite 6. Concentration difficulties 7. Lassitude 8. Inability to feel 9. Pessimistic thoughts 10. Suicidal thoughts Usual cutoff points are: 0 to 6 - normal[5] /symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression |
Screening, week 0, week 2, week 4, week 8 and week 10
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Jon-Kar Zubieta, MD, PhD, University of Michigan
Publications and helpful links
General Publications
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Behavioral Symptoms
- Depression
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Psychotropic Drugs
- Serotonin Uptake Inhibitors
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Serotonin Agents
- Antidepressive Agents, Second-Generation
- Citalopram
- Antidepressive Agents
Other Study ID Numbers
- HUM00033328
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Depression
-
ProgenaBiomeRecruitingDepression | Depression, Postpartum | Depression, Anxiety | Depression Moderate | Depression Severe | Clinical Depression | Depression in Remission | Depression, Endogenous | Depression ChronicUnited States
-
Washington University School of MedicineCompletedTreatment Resistant Depression | Late Life Depression | Geriatric Depression | Refractory Depression | Therapy-Resistant DepressionUnited States, Canada
-
Kintsugi Mindful Wellness, Inc.Sonar Strategies; Vituity PsychiatryRecruitingDepression | Depression Moderate | Depression Severe | Depression MildUnited States
-
University of California, San FranciscoRecruitingDepression Moderate | Depression Mild | Depression, TeenUnited States
-
University GhentUniversiteit Antwerpen; Janssen-Cilag Ltd.RecruitingDepression Moderate | Depression Severe | Depression MildBelgium
-
Baylor College of MedicineUniversity of TexasRecruitingDepression | Depression Moderate | Depression Severe | Suicide and Self-harm | Depression in Adolescence | Depression MildUnited States
-
University of Cape TownNational Institute of Mental Health (NIMH)CompletedPostpartum Depression | Clinical Depression | Moderate DepressionSouth Africa
-
Washington University School of MedicinePatient-Centered Outcomes Research Institute; National Institute of Mental...CompletedMajor Depressive Disorder | Treatment Resistant Depression | Treatment-Refractory Depression | Late Life Depression | Geriatric DepressionUnited States, Canada
-
Gerbera Therapeutics, Inc.Not yet recruitingPostpartum Depression | Depression, Postpartum | Postnatal Depression | Post-partum Depression | Post-Natal DepressionUnited States
-
Lawson Health Research InstituteTerminated
Clinical Trials on Placebo, identified as placebo to participants
-
Dongzhimen Hospital, BeijingCompletedVascular DementiaChina
-
Mackay Memorial HospitalMinistry of Science and Technology, TaiwanCompletedBorderline Personality DisorderTaiwan
-
Institute of Medical Sciences and SUM HospitalNot yet recruitingFunctional Constipation | Constipation - Functional | Constipation Chronic Idiopathic | Fecal Impaction | Pediatric Functional ConstipationIndia
-
AlloVirCompletedBK Virus Infection | BK Virus NephropathyUnited States
-
Janssen Research & Development, LLCCompletedHealthy Volunteers and AsthmaUnited Kingdom, Canada, Netherlands, Germany, Denmark, Belgium
-
Alzheimer's Disease Expert Lab (ADEL), Inc.Oscotec Inc.Recruiting
-
University of ValenciaRecruitingPatellar TendinopathySpain
-
Centocor, Inc.CompletedDiabetes Mellitus, Type 2United States
-
InQpharm GroupCompletedUpper Respiratory Tract SymptomsGermany
-
InQpharm GroupWithdrawn