Placebo Impacts Sleep and Pain Modulation in Chronic Pain

NCT ID: NCT06225817

Last Updated: 2025-06-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 111 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-21
• Study Completion Date: 2027-07-30

Brief Summary

The goal of this free-choice parallel design clinical trial is to examine the potential beneficial effects of using open-label placebo (OLP) in improving chronic pain related outcomes and sleep quality in people with temporomandibular disorders. This study will enroll a cohort of participants with temporomandibular disorders (TMD) which lasts for more than 3 months. The main questions it aims to answer are:

1. Will participants with TMD be more likely to take open-label placebo pills if they are introduced to the effects of placebo (e.g., going through an expectation management session)?

2. Will taking open-label placebo plus expectation management improve chronic pain related outcomes, such as chronic pain intensity, interference, levels of anxiety and depression, in the cohort of TMD?

3. Will open-label placebo plus expectation management improve sleep quality in participants suffering from TMD?

To answer the above questions, participants with TMD will be randomly assigned to three groups: 1. Open-label placebo plus expectation management group, where participants will complete a 1-hour discussion session about their expectations toward open-lable placebo intervention, and then take 1 open-labe placebo pill per day for a total of 45 days. 2. Open-label placebo only group where participants will be asked to take open-label placebo pills, one pill per day, for a total of 45 days. 3. standard of care group where participants will maintain their usual care without introducing open-label placebo to them during the 45 days monitoring. Researchers will compare the chronic pain intensity, interference, mood, anxiety, and sleep quality between the open-label placebo group and the wait-list group. Daily chronic pain will be measured using visual analog scale (VAS) ranging from 0=no pain at all to 100=maximum tolerable pain. Chronic pain interference using Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference and pain behavior. Anxiety and depression will be measured using PROMIS-anxiety, and PROMIS-depression scales respectively. Finally, sleep quality will be quantified using the objective measurement Motion Watch during the 45 days intervention and monitoring. In order to have a rigorous measurement of the baseline pain and sleep fluctuation, this study will include a 7-day phenotyping period before the starting of the 45-day intervention and monitoring. During the 7-day phenotyping period, participants will record their daily chronic pain and sleep quality using polysomnography.

Detailed Description

This is a longitudinal parallel randomized clinical trial with TMD participants randomly assigned to either 1) the open-label placebo (OLP) + expectations management group, 2) OLP only, and 3) the standard of care group. To examine how baseline chronic pain and sleep patterns could have impacted the effects of OLP, we will deep-phenotype participants based on their sleep profiles and fluctuations in their chronic pain characteristics via a 2-day phenotyping phase. Following the 2-day phenotyping phase, participants will enter a 45-day intervention phase. The nature of the participation will be voluntary. Namely, participants can withdraw during trial from the study without any consequences.

Phenotyping phase (2-day) The phenotyping phase includes an in-person visit and a 2-day at-home monitoring period. During the in-person visit, after signing the informed consent form with the trained staff, participants will complete a heat pain sensitivity test using a 30mmx30mm Advanced Thermal Stimulator (ATS) via the Medoc Pathway system (Medoc Advanced Medical Systems, Medoc Ltd., Israel). Painful and non-painful stimuli will be delivered to the ventral forearm of the non-dominant hand.

After the in-person visit, participants will enter a 2-day daily monitoring period, where their daily pain expectations, pain experience fluctuations, and sleep diaries will be assessed in real time and in their natural environment using the Ecological Momentary Assessment (EMA) method. Sleep profiles will be assessed using polysomnography to obtain natural sleep architectures, including the duration of different sleep stages, sleep efficiency, breathing, and body movement during sleep.

Free-choice OLP intervention Immediately following the phenotyping phase, participants will return to the laboratory before entering the 45-day intervention phase. Participants will be randomized to either 1. OLP+expectations management, 2. OLP alone, and 3. Standard of care groups. Participants in the two OLP groups will receive a bottle of 45 OLP pills. According to the free-choice paradigm, participants in the OLP group are allowed to choose whether to take the pills each day during the intervention. This paradigm maximizes participant benefit because it provides the option of "not" taking the placebo pills. Participants in the wait-list group will not receive OLP pills until the end of the 45-day monitoring period.

Conditions

Chronic Pain; Headache

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Open label placebo only arm

Participants who are assigned to the OLP group will be given a bottle of OLP pills. They will be asked to take one pill per day for 45 days. They will be introduced to placebo effects and the therapeutic potential of using open-label placebo for chronic pain management and sleep improvement.

Group Type: EXPERIMENTAL

Open-label placebo pills

Intervention Type: DIETARY_SUPPLEMENT

The placebo pills in this study are empty capsules without any ingredients inside. The capsules are made of microcrystalline cellulose.

Wait-list arm

Participants in the wait-list group will not receive OLP pills until the end of the 45-day monitoring period. Therefore, the 45 days without OLP will serve as an no intervention comparators relative to the OLP group.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Open label placebo + expectation management

Participants assigned to this arm will complete an 1 hour discussion about their expectations towards open-label placebo intervention. After that, they will continue with the 2-day run-in period and 45-day intervention. They will be asked to take 1 open-label placebo pill per day, for a total of 45 days.

Group Type: EXPERIMENTAL

Open-label placebo pills

Intervention Type: DIETARY_SUPPLEMENT

The placebo pills in this study are empty capsules without any ingredients inside. The capsules are made of microcrystalline cellulose.

Interventions

Open-label placebo pills

The placebo pills in this study are empty capsules without any ingredients inside. The capsules are made of microcrystalline cellulose.

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

Zeebo pills

Eligibility Criteria

Inclusion Criteria

• Age ( 18-88 years old)
• English speaker (written and spoken)
• TMD for at least 3 months
• Grade Chronic Pain Scale (GCPS) ≥1
• Smartphone/text messaging capability

Exclusion Criteria

• Present or past degenerative neuromuscular disease
• Cardiovascular, neurological diseases, pulmonary abnormalities, kidney disease, liver disease, history of cancer within past 3 years
• Any personal (or family first degree) history of mania, schizophrenia, or other psychoses
• Severe psychiatric condition (e.g. schizophrenia, bipolar disorders, autism) leading to hospitalization within the last 3 years.
• Lifetime alcohol/drug dependence or alcohol/drug abuse in past 3 months
• Pregnancy or breast feeding
• Impaired or uncorrected hearing

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 88 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Maryland, Baltimore

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Maryland Baltimore School of Nursing

Baltimore, Maryland, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Yang Wang, PhD

Role: CONTACT

yang.wang@umaryland.edu

4107067824

Facility Contacts

Yang Wang, PhD

Role: primary

yang.wang@umaryland.edu

410-706-7824

Rachel Massalee, MS

Role: backup

rmassalee@umaryland.edu

4107065975

Other Identifiers

HP-00105618

Identifier Type: -

Identifier Source: org_study_id