Effects of Open-label Placebos on COVID-related Psychological Health

Study Overview
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Brief Summary
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This project aimed to test the efficacy of a telehealth-administered placebo without deception intervention on stress, anxiety, and depression related to the COVID-19 pandemic. Participants were randomized into two groups (open-label placebo vs. no-treatment control). All participants received information on the impact of COVID-19 on psychological health. Participants in the open-label placebo group were instructed to watch an informational video on the beneficial effects of placebos without deception, remotely interact with an experimenter, and take open-label placebo pills twice a day for two weeks. Participants in the no-treatment control group did not receive any intervention. Instead, participants met with an experimenter and reported on their psychological and physical health. The investigators predicted that the placebo without deception group would exhibit substantially reduced stress, depression, and anxiety compared to a no-treatment control group.

Official Title
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Effects of Open-label Placebos Administered Through Telehealth on COVID-related Stress, Anxiety, and Depression

Conditions
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Stress, Anxiety, Depression

Intervention / Treatment
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* Behavioral: Non-Deceptive Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals who have experienced moderate COVID-19 stress, as assessed by a score of ≥ 35 on the COVID-19 Stress Scale (Taylor et al., 2020). Exclusion Criteria: Non-Michigan residents; self-reported diagnosis of anxiety, depression, ADHD, schizophrenia, bipolar disorder, substance use disorder; currently taking psychotropic medication including antidepressants, anti-anxiety medication or stimulants; allergies or concerns with the placebo pill ingredients; or active diagnosis of COVID-19 at the time of eligibility or enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Non-Deceptive Placebo<br>The NDP group was informed that the purpose of the study was to test a mind-body intervention that might help participants deal with the stress and anxiety that they are feeling during the pandemic. The intervention included two videos that introduced the effects of non-deceptive placebos, followed by a presentation on up-to-date non-deceptive placebo research. The participants then received instruction on how they would take their non-deceptive placebos for the next two weeks. Participants were asked to complete daily pill-taking adherence surveys ( 5 min) and weekly at midpoint (1-week) and endpoint (2-week). | Behavioral: Non-Deceptive Placebo<br>* The placebos were ordered through Amazon from Zeebo® (Zeebo, Zeebo Effect, LLC, South Burlington, Vermont, USA). The placebos in this study were blue and white capsules containing Microcrystalline cellulose (an inert fiber). Ingredients include ones that are typically used to make pills including silica, gelatin, titanium dioxide, red #3 food coloring, and blue #1 food coloring. Placebo capsules were free of any active ingredients. These bottles were not branded specifically for the experiment, including the brand name (Zeebo Relief), description of the contents, directions, and a disclaimer. The investigators chose to not include a custom label for transparency and in order to increase non-deceptive placebo effects. Participants were instructed to take two pills a day, one in the morning and one in the evening.<br>|
| No Intervention: No-Treatment Control<br>The Control group did not receive an intervention. Instead, participants were informed that the purpose of the study was to track individual psychological and physical health over longer time periods in the context of the pandemic. Participants were asked to complete weekly questionnaires at midpoint (1-week) and endpoint (2-week). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| COVID-19 related stress | Self-reported COVID-19 related stress was measured using the COVID-19 Stress Scale. The Covid stress scale (CSS) is a 36-item self-report questionnaire that measures stress related to COVID-19 across various subscales (danger and contamination, socioeconomic consequences, xenophobia, traumatic stress, and compulsive checking; Taylor et al., 2020). | Changes in COVID-19 related stress were measured at mid-point (1-week) and end-point (2-weeks) relative to baseline COVID-19 related stress. | 
| Perceived Stress | Self-reported perceived stress was measured using the Perceived Stress Scale (PSS). The Perceived Stress Scale (PSS) is a 10-item self-report questionnaire which assesses the extent to which different situations affect our perceptions of stress during the last month (Cohen, 1994). The scale was modified for the current study in order to measure ratings of perceived stress over the past 7 days. | Changes in Perceived stress were measured at mid-point (1-week) and end-point (2-weeks) relative to baseline perceived stress. | 
| Anxiety | Self-reported anxiety was measured using the PROMIS Emotional Distress - Anxiety - Short Form. The PROMIS Emotional Distress - Anxiety - Short Form is an 8-item self-report questionnaire that assesses anxiety over the past 7 days in adults. | Changes in anxiety symptom severity were measured at mid-point (1-week) and end-point (2-weeks) relative to baseline anxiety. | 
| Depression | Self-reported anxiety was measured using the Center for Epidemiological Studies - Depression (CES-D) Scale. The Center for Epidemiological Studies - Depression (CES-D) Scale is a 20-item self-report questionnaire that assesses depressive symptoms over the past 7 days. | Changes in depression symptom severity were measured at mid-point (1-week) and end-point (2-weeks) relative to baseline depression. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment expectations | Participants in the open-label placebo group rated their expectations of the open-label placebo treatment using representative questions (10-items) from each sub-scale of the Treatment Expectations Questionnaire (TEX-Q; Alberts et al. (2020). | Treatment expectations were measured during the administration of the intervention (Day 1). | 
| Treatment adherence | Participants in the open-label placebo group were instructed to take two placebo pills a day for 14 days (28 placebo pills). Treatment adherence was measured as the percentage of placebo pills taken by each participant (number of pills taken / 28). | Treatment adherence was measured daily for 14 days beginning after intervention administration (Day 1). | 
| Intervention Feasibility | Intervention feasibility was measured using the Feasibility of Intervention Measure (FIM; Weiner et al., 2017). The FIM is a 4-item self-report measure that assesses the extent to which an intervention can be successfully implemented within a given setting. | Ratings of intervention feasibility were measured at endpoint (2 weeks post baseline) upon completion of the intervention. | 
| Intervention Acceptability | Intervention acceptability was measured using the Acceptability of Intervention Measure (AIM; Weiner et al., 2017). The AIM is a 4-item self-report measure that assesses the extent to which an intervention is perceived to be satisfactory, adequate, and appealing. | Ratings of intervention acceptability were measured at endpoint (2 weeks post baseline) upon completion of the intervention. | 
| Intervention Appropriateness | Intervention appropriateness was measured using the Intervention Appropriateness Measure (IAM; Weiner et al., 2017). The IAM is a 4-item self-report measure that assesses the extent to which an intervention is perceived to be fitting, relevant, and compatible with a population or setting to address a particular problem. | Ratings of intervention appropriateness were measured at endpoint (2 weeks post baseline) upon completion of the intervention. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Non-Deceptive Placebos, Intervention, Telehealth, Stress, Anxiety, Depression