An interventional study of Non-deceptive placebo (NDP) in Depression - Major Depressive Disorder, Psychological Distress and Depression / Major Depressive Disorder, sponsored by Miami University. Not yet recruiting at 1 site in United States. Open to participants aged 18 Years to 30 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-10-22.
Sponsored by Miami University · Not applicable, Interventional, and Treatment
Subclinical depression - depressive symptoms that fall below the threshold for major depressive disorder - is common in young adults and predicts later depressive episodes, yet it often goes untreated. This study tests whether a brief, remotely delivered non-deceptive (open-label) placebo intervention reduces subclinical depressive symptoms over approximately two weeks.
Participants aged 18-30 living in Ohio, with PHQ-8 scores in the 5-9 range, are randomly assigned to one of three groups: a non-deceptive placebo group, a blinded control group, or an unblinded control group. All participants complete three remote sessions over 16-18 days and complete the same assessments on the same schedule. Participants in the non-deceptive placebo group additionally receive psychoeducation about placebo effects and placebo pills that are explicitly described as containing no active ingredients, which they take twice daily for two weeks. Participants in the unblinded control group are told they have been assigned to a control condition. Participants in the blinded control group are not told their group assignment until debriefing at the end of the study.
The study has two aims. The first is to estimate the effect of the non-deceptive placebo intervention on depressive symptoms and related outcomes. The second is methodological: to determine whether telling control participants that they are in a control group changes their outcomes, and therefore whether the choice of control condition systematically biases estimates of non-deceptive placebo effects.
Non-deceptive (open-label) placebos have been shown to reduce negative emotion, stress, anxiety, and depressive symptoms across a range of nonclinical samples. Because the intervention requires explicitly telling participants that the pills contain no active ingredients, participants cannot be blinded to the intervention. This creates an unresolved methodological problem: there is no consensus on the appropriate comparison condition. Some trials use unblinded assessment-only controls, which prioritize transparency but may introduce negative expectancy or demoralization and inflate apparent intervention effects. Others use blinded controls, which may better isolate expectancy mechanisms but raise concerns about incomplete disclosure. Few studies have compared the two within a single randomized design.
This trial is a remote, parallel-group randomized controlled trial in young adults with subclinical depressive symptoms. Eligible participants are randomized in blocks of 30 to one of three arms, with allocation distributed evenly across conditions. Randomization occurs after eligibility confirmation and before the first live session, because arm assignment determines which enrollment consent form is presented and because the placebo arm requires materials to be mailed in advance.
The study is conducted entirely remotely using Qualtrics for survey administration and Webex for live sessions, across four phases spanning approximately 16-18 days:
Day 0 (Screening): Online screening consent followed by an eligibility survey covering demographics, PHQ-8, and feasibility items.
Day 1 (Enrollment, \~60 min, Webex Session 1): Eligibility is confirmed, participants complete arm-specific enrollment consent, and a battery of individual difference measures assessing worry, trait anxiety, dispositional optimism, personality, emotion regulation, and implicit theories of anxiety, depression, and trauma.
Days 3-5 (Baseline/Time 1, \~60 min, Webex Session 2): All participants complete baseline outcome measures, then receive a standardized presentation on the prevalence of stress, anxiety, and depressive symptoms. Participants in the non-deceptive placebo arm then receive the intervention: two brief psychoeducational videos on placebos and non-deceptive placebo effects with comprehension and expectancy items, followed by instructions for twice-daily pill intake over the following two weeks and for completing a brief daily pill-tracking survey. Participants in the unblinded control arm are informed of their control status. Participants in the two control arms receive no placebo psychoeducation and no pills.
Days 16-18 (Endpoint/Time 2, \~60 min, Webex Session 3): All participants complete endpoint outcome measures and open-ended feedback items and receive a full debriefing describing the study conditions and their own assignment. Participants in the blinded control arm are explicitly informed that the study involved incomplete disclosure and given the rationale, and may request withdrawal of their data.
The primary analysis will use a mixed model for repeated measures with planned orthogonal contrasts: the non-deceptive placebo arm versus the average of the two control arms (Aim 1), and the blinded versus unblinded control arms (Aim 2).
8,240 studies on the registry are indexed under Depression; 1,641 are open to participants now.
This study's planned enrollment of 330 is above the median of 84 across 6,869 interventional studies indexed under Depression.
Browse Depression studies →Miami University is the lead sponsor of 12 studies on the registry; 3 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Participants complete the same assessments and receive the same placebo psychoeducation content as the intervention arm, but receive no pills. They are not informed of their group assignment or of the existence of other study arms until debriefing at endpoint.
Participants complete the same assessments on the same schedule as the intervention arm but receive no intervention. They are explicitly informed at the baseline session that they have been assigned to a control condition and will not receive the intervention.
Psychoeducation about placebo effects, consisting of two brief videos ("Placebos \& the Placebo Effect" and "Placebos Can Work Without Deception") with a minimum viewing time and written comprehension summaries, plus an experimenter-delivered summary of evidence that non-deceptive placebos can reduce emotional distress. Participants also receive inert tablets containing no active pharmaceutical ingredient (microcrystalline cellulose and vegetable-grade stearate; Zeebo Effect LLC), explicitly described as containing no active medicine, mailed in advance and taken twice daily for approximately two weeks, with adherence recorded via a brief daily yes/no tracking survey.
Other: Non-deceptive placebo (NDP)
Participants are explicitly informed that they are in a study of placebo effects and that the pills they receive contain no active ingredients. They receive psychoeducation about placebo effects and open-label placebo tablets (Zeebo Effect LLC; microcrystalline cellulose with a small amount of vegetable-grade stearate), mailed in advance, to be taken twice daily for approximately two weeks, along with a brief daily pill-tracking survey.
Also known as: open-label placebo
Change in depressive symptoms (PHQ-8)
Patient Health Questionnaire, 8-item depression scale (Kroenke et al., 2009). Total score range 0-24, with higher scores indicating greater depressive symptom severity.
Time frame: Baseline to endpoint at 2 weeks.
Treatment expectancy
First three items of the Treatment Expectation Questionnaire (TEX-Q; Shedden-Mora et al., 2023), corresponding to the positive treatment outcome expectation subscale: expected symptom relief, expected benefit, and expected health improvement. Each item is rated on an 11-point scale from 0 to 10, with higher scores indicating stronger positive expectations. Scored as the mean of the three items.
Time frame: Immediately after intervention delivery at the baseline session
Intervention acceptability
Acceptability of Intervention Measure (AIM; Weiner et al., 2017). Four items rated from 1 (completely disagree) to 5 (completely agree), scored as the mean of the four items. Score range 1-5; higher scores indicate greater acceptability of the intervention.
Time frame: Endpoint, 2 weeks after baseline
Intervention appropriateness
Intervention Appropriateness Measure (IAM; Weiner et al., 2017). Four items rated from 1 (completely disagree) to 5 (completely agree), scored as the mean of the four items. Score range 1-5; higher scores indicate greater perceived appropriateness of the intervention.
Time frame: Endpoint, 2 weeks after baseline
Intervention feasibility
Feasibility of Intervention Measure (FIM; Weiner et al., 2017). Four items rated from 1 (completely disagree) to 5 (completely agree), scored as the mean of the four items. Score range 1-5; higher scores indicate greater perceived feasibility of the intervention.
Time frame: Endpoint, 2 weeks after baseline
Plan to share: Yes — De-identified individual participant data underlying published results may be shared for replication, secondary analysis, and publication purposes, consistent with Miami University data management policies. Data will be stripped of any information that could reasonably identify a participant. Data will be retained for up to five years after study completion.
Supporting information: Study protocol, Statistical analysis plan, Analytic code
Time frame: IPD and supporting documentation will be available beginning 12 months after publication of the primary results.
Access criteria: De-identified data, the study protocol, the statistical analysis plan, and analytic code will be deposited in a public repository at the time of primary publication and made available without restriction for any purpose. Where repository deposit is not possible, data will be available on request to the Principal Investigator (guevarda@miamioh.edu); requests will be reviewed by the study team and released under a data use agreement specifying that no attempt will be made to re-identify participants.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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