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

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

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.

Study Overview

• Status: Completed
• Conditions: Depression; Stress; Anxiety
• Intervention / Treatment: Behavioral: Non-Deceptive Placebo

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Michigan
    • East Lansing, Michigan, United States, 48823
      • Michigan State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 28 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Non-Deceptive Placebo; 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; 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.
No Intervention: No-Treatment Control; 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?

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 (Taylor et al., 2020). Participants rated each item on a 0 (not at all) to 4 (extremely) scale. For the purposes of this study, only total scores were calculated. Total score ranges from 0-144 with higher scores indicating greater COVID-related stress.	COVID-19 related stress was measured at Baseline (Day 1), Midpoint (Day 7), and Endpoint (Day 14)
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 that 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. Participants rated each item on a 0 (never) to 4 (very often) scale. Total score ranges from 0-40 with higher scores indicating greater perceived stress.	Perceived stress measured at Baseline (Day 1), Midpoint (Day 7), and Endpoint (Day 14)
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. Participants rated each item on a 1 (never) to 4 (always) scale. Total score ranges from 8-40 with higher scores indicating greater anxiety.	Anxiety symptom severity was measured at Baseline (Day 1), Midpoint (Day 7), and Endpoint (Day 14)
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. Participants rated each item on a 0 [rarely or none at the time (less than one day)] to 3 [most or all of the time (5 to 7 days)] scale. Total score ranges from 0-60 with higher scores indicating higher levels of depression.	Depression symptom severity was measured at Baseline (Day 1), Midpoint (Day 7), and Endpoint (Day 14)

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). Two subscales were calculated from exploratory factor analysis: Expected benefits and Expected harm. The range for expected benefits ranged from 0-10 with higher scores indicating greater benefits from the OLP. The range for expected harm also ranged from 0-10 with higher scores indicating expecting more harm.	Treatment expectations were measured during the administration of the intervention (Day 1) and at the end of the study (Day 14)
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 * 100).	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. The items are averaged with scores ranging from 1-5 with higher numbers indicating that the OLP intervention is easy to use and doable.	Ratings of intervention feasibility were measured at Endpoint (Day 14)
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. The items are averaged with scores ranging from 1-5 with higher numbers indicating that the OLP intervention is satisfactory and appealing.	Ratings of intervention acceptability were measured at Endpoint (Day 14)
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. The items are averaged with scores ranging from 1-5 with higher numbers indicating that the OLP 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 (Day 14)

Collaborators and Investigators

• Sponsor: Michigan State University
• Investigators: Principal Investigator: Jason S Moser, Ph.D., Michigan State University

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2021
• Primary Completion (Actual): May 5, 2021
• Study Completion (Actual): May 5, 2021

Study Registration Dates

• First Submitted: August 12, 2021
• First Submitted That Met QC Criteria: September 2, 2021
• First Posted (Actual): September 5, 2021

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Depression; Anxiety; Stress; COVID-19; Telehealth; Intervention; Non-Deceptive Placebos
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Anxiety Disorders
• Other Study ID Numbers: NDP00004435

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The investigators plan to share the IPD used in the analysis for manuscript submission.
• IPD Sharing Time Frame: IPD will be available one year after publication
• IPD Sharing Access Criteria: IPD will be available upon request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No