A Neuroimaging Study of Open-label Placebo in Depressed Adolescents

NCT04201106 | Active Not Recruiting

• 2 other identifiers: 19-29443R61AT012028
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Major depressive disorder (MDD) is the current leading cause of disability worldwide and adolescence is an especially vulnerable period for the onset of depression. Non-pharmacologic approaches are particularly attractive as treatment of adolescent depression due to the elevated risks of side effects related to the use of psychotropic drugs during development. A recent meta-analysis detected a positive and significant effect of non-deceptive placebos (open-label placebo, OLP) for a series of clinical conditions, including adult depression. To the investigators' knowledge, no studies of OLP have been conducted in depressed adolescents to date, although placebo response rates in adolescent depression are especially high, accounting for over 80% of the actual response to antidepressant treatment. The study's main objective is to estimate the effectiveness and understand the mechanism of OLP in depressed adolescents. The central hypothesis is that the mechanism by which OLP exerts its action in adolescent depression is by forming a positive expectation, which activates endogenous mu-opioid receptor (MOR)-mediated neurotransmission in a network of regions implicated in emotion, stress regulation, and the pathophysiology of MDD, namely, the anterior cingulate cortex (ACC) - striato - amygdalo - thalamic network. The hypothesis has been formulated on the basis of published research and preliminary data. The investigators will test the hypothesis by performing structural and functional neuroimaging in 60 untreated 13-18 year-old adolescents with mild to moderate depression. The proposed research is significant, because it is expected to elucidate the mechanism of action of OLP and advance the understanding of the neural underpinnings of positive expectations in adolescent depression.

Conditions

Depression

Keywords

Placebo; Adolescent Depression; MRI

Outcome Measures

Primary Outcomes (2)

• Change in Reynolds Adolescent Depression Scale (RADS-2) Scores

  The investigators will be looking at changes in the RADS-2 scores scores. RADS-2 was selected as the primary clinical outcome measure because it is a widely used, well-established, and standardized self-report measure of adolescent depression. The RADS-2 has a possible range of 30 to 120. Higher scores represent higher levels of depression.

  Baseline and 2 weeks post baseline

• The cerebral blood perfusion (CBP) in the anterior cingulate cortex (ACC)- striato - amygdalo - thalamic network

  Blood perfusion in a network of regions implicated in emotion, stress regulation, and the pathophysiology of depression, measured using MRI, specifically, an MRI technique known as arterial spin labeling (ASL).

  At Baseline

Secondary Outcomes (2)

• Change in structural connectivity of the ACC - striato - amygdalo - thalamic network

  Baseline and at 2 weeks post baseline

• Change in functional connectivity of the ACC - striato - amygdalo - thalamic network

  Baseline and at 2 weeks post baseline

Study Arms (3)

Control

NO INTERVENTION

In the control group, the participants will not be taking any placebos or undergoing any other study-related treatments.

Open Label Placebo Group with Rationale

EXPERIMENTAL

Behavioral: Open Label Placebo with Rationale

Open Label Placebo Group without Rationale

ACTIVE COMPARATOR

Behavioral: Open Label Placebo without Rationale

Interventions

Open Label Placebo with Rationale BEHAVIORAL

In the OLP + rationale group, the participants will be prescribed to take placebos for 2 weeks with the standard 4-point accompanying rationale: (1) the placebo effect is powerful, e.g. in clinical trials placebos are roughly 80% as effective as antidepressants; (2) classical conditioning is a possible mechanism for automatic self-healing - meaning that the body can automatically respond to taking placebo pills like Pavlov's dogs who salivated when they heard a bell; (3) placebo-treated patients who are more compliant have better outcomes, therefore the placebos should be taken faithfully; and (4) positive expectations increase placebo effects, but it is OK to have doubts.

Open Label Placebo Group with Rationale

Open Label Placebo without Rationale BEHAVIORAL

In the OLP without rationale group, the adolescents will be asked to take placebos for 2 weeks but they will be told that the pills contain inert substance and do not have any pharmacological effect.

Open Label Placebo Group without Rationale

Eligibility Criteria

• Age: 13 Years - 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• The investigators will include adolescents with mild to moderate depression who meet the following criteria.
• Unmedicated 13-18 year-old adolescents of both sexes with mild to moderate depression, i.e. depressive symptoms corresponding to RADS-2 t-scores of 61-69, under the care of a mental health professional or a primary care doctor.
• Fluency in English

You may not qualify if:

• Subjects younger or older than 13-18 years old.
• Psychiatric comorbidities other than anxiety disorder, severe suicidal ideation
• MRI contraindications (ferromagnetic objects on or inside the body, e.g. braces) and pregnancy.
• Potential subjects with an inability or unwillingness to give written informed assent whose legal guardian/representative are unable or unwilling to give written informed consent will be excluded and not allowed to enroll in the study.

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Center for Complementary and Integrative Health (NCCIH): collaborator

Study Sites (1)

UCSF

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Depression

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Study Officials

• Tony T Yang, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2019
• First Posted: December 17, 2019
• Study Start: May 14, 2020
• Primary Completion (Estimated): December 30, 2032
• Study Completion (Estimated): December 30, 2032
• Last Updated: April 13, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)