Clinical trial NCT04724668: The Role of the Circadian System in Binge Eating Disorder
Official title: The Role of the Circadian System in Binge Eating Disorder
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Binge-Eating Disorder
Circadian Rhythm Disorders
Keywords: Binge eating
Circadian
Lead sponsor: University of Cincinnati
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
name: Lindner Center of HOPE
First posted: 2021-01-26
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The specific aims will be completed in a two-phase experimental approach. In the first phase (specific aim 1), obese subjects with BED (n=40) and without BED (n=40) will participate in a 2-week longitudinal study. In the second phase (specific aim 2), only BED subjects that complete phase 1 will rollover for a 4-week intervention study.
Primary purpose: BASIC_SCIENCE

Brief summary: Binge eating disorder (BED) shows prominent circadian features that suggest a delay in circadian phase, and preliminary evidence shows binge eating may be responsive to chronobiological interventions, implicating a circadian system dysfunction in its pathophysiology. What remains lacking, however, is comprehensive knowledge of the characteristics of circadian system dysfunction in BED, and whether this dysfunction represents a therapeutic target in BED. There is therefore a critical need to characterize circadian system dysfunction in BED, and evaluate it as a potential therapeutic target. Without such information, the understanding on the role of the circadian system in BED and its potential as a new therapeutic target will remain limited.

Detailed description: The overall objective of the research strategy will be to characterize circadian system dysfunction in BED and its potential as a therapeutic target. The central hypothesis is that a circadian system dysfunction (phase delay) plays a role in the pathophysiology of BED, and that advancing the circadian phase will improve BED symptoms. To attain the overall objectives, the following specific aims will be pursued in two phases:

Specific aim 1) To characterize circadian system dysfunction in BED (Phase 1). Circadian system function will be evaluated in 80 adult (18 to 50yrs) obese subjects, 40 with BED and 40 without BED as a control group matched by age, body mass index (BMI), and gender, during a two-week observational phase. Based on preliminary data, the working hypothesis is that DLMO (the primary outcome measure) and secondary circadian parameters (i.e., locomotor activity acrophase) will occur later in the BED group compared with the control group, and a later circadian phase will be associated with worse BED clinical features.

Specific aim 2) To evaluate circadian phase as a predictive biomarker for response to a chronobiological intervention and evidence of circadian system target engagement in BED (Phase 2). A mechanistic clinical trial with a 4-week double-blinded, randomized, sham/placebo controlled study design will evaluate the effect of a combination of morning lights+Melatonin/placebo on the circadian system and eating behavior on 40 BED subjects that complete phase 1. Subjects will be randomized to receive a combination of morning lights at usual wake time + Melatonin(3mg) or placebo (3hr before DLMO). Based on preliminary data, the working hypothesis is that a chronobiological intervention will induce a greater DLMO advance (primary outcome measure), greater decrease in binge eating days/week (secondary outcome measure), and change in exploratory metabolic outcomes. In addition, a later baseline DLMO (secondary outcome) will predict change in binge eating days/week and metabolic parameters in response to a chronobiological intervention.

Eligibility criteria: Binge Eating Disorder (BED) group inclusion criteria:

1. Age 18-50 years, inclusive
2. Female or male
3. BMI ≥30 kg/m2
4. Current BED diagnoses by Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) criteria confirmed by Structured Clinical Interview (SCID-5)
5. Moderate or severe BED (≥3 binge eating episodes/week in the past 14 days)
6. No current pharmacological treatment for BED, or if receiving treatment dose stable for ≥ 2 months
7. If receiving psychotherapy, intervention must be stable for ≥ 3 months and agree to continue during the study
8. Other psychiatric disorders will be permitted as long as they are not more than moderate in severity
9. Using an effective contraceptive method (participants of childbearing potential)

BED exclusion criteria:

1. Current severe comorbid psychopathology (i.e; mania, severe major depressive disorder (MDD), psychosis)
2. Current (past month) substance use disorder (caffeine and nicotine allowed)
3. Chronic use of bright light therapy (BLT) or melatonin in the past month
4. Current contraindication or history of melatonin allergy or non-tolerability;
5. Current contraindication or history of BLT non-tolerability
6. Significant risk of suicide according to Columbia-Suicide Severity Rating Scale (CSSRS) or clinical judgment, or suicidal behavior in the past year
7. Routine shift work (night work) in the past month
8. Travel across more than 1 time zone in the past two weeks
9. Current treatment with medication known to affect the circadian system or melatonin measurements, including: B-blockers, hypnotic sedatives, anticoagulants, antidiabetes drugs, oral corticosteroids, and other immunosuppressant medication
10. Current lesions or bleeding in the oral cavity, as it may alter DLMO measurements
11. Clinically significant unstable medical conditions as judged by the clinician, including: seizure or neurodegenerative disorders, thyroid conditions, autoimmune disorders, and cardiovascular disease
12. Pregnancy or breastfeeding
13. Participation in a clinical trial in the past month
14. Suspected intelligence quotient (IQ) \<80
15. Any other clinically relevant reason as judged by the clinician

Control group inclusion criteria:

1. Age 18-50 years, inclusive
2. Female or male;
3. BMI ≥30 kg/m2
4. No current or lifetime history of BED or bulimia nervosa diagnoses confirmed by SCID-5
5. No current (past month) psychiatric diagnosis according to SCID-5, including substance use disorders (caffeine and nicotine allowed)
6. No current psychiatric or psychological treatment, or if receiving treatment dose/intervention stable for ≥ 2 months

Control group exclusion criteria:

1. Clinically significant unstable medical conditions as judged by the clinician, including: seizure or neurodegenerative disorders, thyroid conditions, autoimmune disorders, and cardiovascular disease
2. Chronic treatment with BLT or melatonin in the past month
3. Routine shift work (work at night) in the past month
4. Travel across more than 1 time zone in the past two weeks
5. Significant risk of suicide according to CSSRS or clinical judgment, or suicidal behavior in the past year
6. Current treatment with medication known to affect the circadian system or melatonin measurements, including, B-blockers, hypnotic sedatives, anticoagulants, antidiabetes drugs, oral corticosteroids, and other immunosuppressant medication
7. Current lesions or bleeding in the oral cavity, as it may alter DLMO measurements
8. Pregnant or breastfeeding
9. Participation in a clinical trial in the past month
10. Suspected IQ\<80
11. Any other clinically relevant reason as judged by the clinician

Primary outcomes:
measure: Phase 1 Dim Light Melatonin Onset (DLMO)
timeFrame: Phase 1 baseline (visit 0)
measure: Phase 2 Dim Light Melatonin Onset (DLMO)
timeFrame: Phase 2 baseline (visit 0) to endpoint, on average one month.
Secondary outcomes:
measure: Phase 1 Locomotor activity acrophase
timeFrame: Phase 1 baseline (visit 0)
measure: Phase 1 Midline Estimating Statistic of Rhythm (MESOR)
timeFrame: Phase 1 baseline (visit 0)
measure: Phase 1 MEQ
timeFrame: Phase 1 baseline (visit 0)
measure: Phase 1 Association between DLMO and binge eating days/week
timeFrame: Phase 1 baseline (visit 0)
measure: Phase 2 Binge eating days/week
timeFrame: Phase 2 baseline (visit 0) to endpoint, on average one month.
measure: Phase 2 Locomotor activity acrophase
timeFrame: Phase 2 baseline (visit 0) to endpoint, on average one month.
measure: Phase 2 baseline (visit 0) to endpoint
timeFrame: Phase 2 baseline (visit 0) to endpoint, on average one month.
Other outcomes:
Locations:
city: Mason
country: United States
facility: Lindner Center of HOPE / University of Cincinnati
state: Ohio
Study officials:
affiliation: University of Cincinnati/ Lindner Center of HOPE
name: Francisco Romo-Nava, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: