DepressionPhase 4NCT02178696
Predictors of Antidepressant Response
A Phase 4 study testing Celexa or other antidepressant as clinically indicated in people with Depression, run by University of Michigan at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Depression
- What is being tested?
- Celexa or other antidepressant as clinically indicated
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2011to Oct 2015
- 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 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Participants diagnosed with Major Depressive Disorder and will include Hamilton Depressive Rating Scale (HDRS) scores >15
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
We performed a single-blinded two-week cross-over randomized controlled trial of two identical oral placebos (described as having either potentially "active" fast-acting antidepressant-like effects or to be "inactive") followed by a 10-week open-label treatment with a selective serotonin reuptake inhibitor (SSRI) or in some cases, another agent as clinically indicated. The volunteers were studied with PET and the µ-opioid receptor selective radiotracer [11C]carfentanil after each 1-week "inactive" and "active" oral placebo treatment. In addition, 1 mL of isotonic saline was administered intravenously (i.v.) within sight of the volunteer during PET scanning every 4 min over 20 min only after the 1-week active placebo treatment, with instructions that the compound may be associated with the activation of brain systems involved in mood improvement. This challenge stimulus was utilized to test the individual capacity to acutely activate endogenous opioid neurotransmission under expectations of antidepressant effect.
- Conditions
- Depression
- Being tested
- Placebo, identified as placebo to participants, Celexa or other antidepressant as clinically indicated, Placebo, identifed to participants as "Active medication"
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo, identified as placebo to participantsOther
White tablets
Celexa or other antidepressant as clinically indicatedDrug
Also called S-citalopram 20-40 mg orally
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
Placebo, identifed to participants as "Active medication"Other
Blue Capsule
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Placebo, identified as placebo to participants; Drug: Celexa or other antidepressant as clinically indicated; Other: Placebo, identifed to participants as "Active medication" |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: (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.
Measured: (90 minute fMRI scans) assessed at Weeks 1 and 2
Secondary outcomes (5)
Changes in Dopamine (D 2/3) Binding Potential During PET.
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.
Measured: (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
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.
Measured: From Pre to post- active placebo, and from pre to post- inactive placebo (1 week intervention)
Changes From Baseline in PHQ-9 Depression Scores.
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.
Measured: From Pre to post- active placebo, and from pre to post- inactive placebo (1 week intervention)
Hamilton Depression Rating Scale Scores
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.
Measured: Screening, week 0, week 2, week 4, week 8 and week 10
Montgomery-Asberg Depression Rating Scale
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
Measured: Screening, week 0, week 2, week 4, week 8 and week 10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2014 (estimated)
- Study startJan 2011
- Primary completionOct 2015
- Study completionOct 2015
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 (2)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- 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
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jon-Kar Zubieta, University of Michigan
- Investigators
- Jon-Kar Zubieta, MD, PhD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02178696
- Sponsor's protocol ID
- HUM00033328
- Status last verified
- Oct 2017
- First submitted
- 12 Jun 2014
- Last updated
- 5 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
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.
PubMed 26421634Sikora 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.
PubMed 26709390
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Predictors of Antidepressant Response
- ClinicalTrials.gov ID
- NCT02178696
- Acronym / sponsor ID
- HUM00033328
- Conditions
- Depression
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Study start
- Jan 2011
- Primary completion
- Oct 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 1 Jul 2014 (estimated)
- Results
- Posted 5 Dec 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
We performed a single-blinded two-week cross-over randomized controlled trial of two identical oral placebos (described as having either potentially "active" fast-acting antidepressant-like effects or to be "inactive") followed by a 10-week open-label treatment with a selective serotonin reuptake inhibitor (SSRI) or in some cases, another agent as clinically indicated. The volunteers were studied with PET and the µ-opioid receptor selective radiotracer [11C]carfentanil after each 1-week "inactive" and "active" oral placebo treatment. In addition, 1 mL of isotonic saline was administered intravenously (i.v.) within sight of the volunteer during PET scanning every 4 min over 20 min only after the 1-week active placebo treatment, with instructions that the compound may be associated with the activation of brain systems involved in mood improvement. This challenge stimulus was utilized to test the individual capacity to acutely activate endogenous opioid neurotransmission under expectations of antidepressant effect.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Known Placebo First | Experimental | Other: Placebo, identified as placebo to participants, Drug: Celexa or other antidepressant as clinically indicated, Other: Placebo, identifed to participants as "Active medication"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. |
| "Active" (blinded) Placebo first group | Experimental | Other: Placebo, identified as placebo to participants, Drug: Celexa or other antidepressant as clinically indicated, Other: Placebo, identifed to participants as "Active medication"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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Participants diagnosed with Major Depressive Disorder and will include Hamilton Depressive Rating Scale (HDRS) scores >15
Key exclusion criteria (5 listed)
- 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
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 |
|---|---|---|
| Placebo, identified as placebo to participantsWhite tablets | Other | "Active" (blinded) Placebo first group, Known Placebo First |
| Celexa or other antidepressant as clinically indicatedAlso: S-citalopram 20-40 mg orallyOpen 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 | Drug | "Active" (blinded) Placebo first group, Known Placebo First |
| Placebo, identifed to participants as "Active medication"Blue Capsule | Other | "Active" (blinded) Placebo first group, Known Placebo First |
Primary outcome
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.
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.
5 secondary outcomes
Changes in Dopamine (D 2/3) Binding Potential During PET.
Time frame: (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)
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)
Hamilton Depression Rating Scale Scores
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 26421634Pecina 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.
- Results publication: PubMed 26709390Sikora 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.
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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.
Jon-Kar Zubieta, MD, PhD principal investigator
University of Michigan
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 Celexa or other antidepressant as clinically indicated in people with Depression, run by University of Michigan 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 1 inclusion and 5 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 5 Dec 2017. 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 5 Dec 2017). 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?
Changes in Mu-opioid Binding Potential During PET (time frame: (90 minute PET scans) assessed at Weeks 1 and 2). The study lists 2 primary outcomes in all. 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 NCT02178696, which also lists 2 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 5 Dec 2017; AzTrials last refreshed its copy on 30 Oct 2026.