The Role of the Circadian System in Binge Eating Disorder

Binge-Eating Disorder Clinical Trial

Official title:

The Role of the Circadian System in Binge Eating Disorder

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04724668
• Other study ID #: 2020-0345
• Secondary ID: 1K23MH120503-01A
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 15, 2021
• Est. completion date: June 30, 2024

Study information

• Verified date: May 2023
• Source: University of Cincinnati
• Contact: Georgi Georgiev, MSW
• Phone: 513-536-0707
• Email: georgi.georgiev[@]lindnercenter.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Binge-Eating Disorder
• Bulimia
• Chronobiology Disorders
• Circadian Rhythm Disorders
• Disease
• Feeding and Eating Disorders

Intervention

Dietary Supplement:
• Melatonin (3hrs before DLMO)
Melatonin 3mg (3hrs before DLMO)
• Placebo (3hrs before DLMO)
Placebo capsule (3hrs before DLMO)

Device:
• Morning light version 1
Morning light version
• Morning light version 2
Morning light version

Locations

Country	Name	City	State
United States	Lindner Center of HOPE / University of Cincinnati	Mason	Ohio

Sponsors (3)

Lead Sponsor	Collaborator
University of Cincinnati	Lindner Center of HOPE, National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1 Dim Light Melatonin Onset (DLMO)	Difference in mean DLMO (measured in time) between subjects with binge eating disorder (BED) and control subjects without BED.	Phase 1 baseline (visit 0)
Primary	Phase 2 Dim Light Melatonin Onset (DLMO)	Differences in DLMO (measured in time) change from baseline to endpoint between two intervention groups will be analyzed using an ANCOVA model with age as a covariate.	Phase 2 baseline (visit 0) to endpoint, on average one month.
Secondary	Phase 1 Locomotor activity acrophase	Difference in mean locomotor activity acrophase (7 days) measured in time between BED and control subjects without BED	Phase 1 baseline (visit 0)
Secondary	Phase 1 Midline Estimating Statistic of Rhythm (MESOR)	Difference in mean MESOR (7 days) measured in time between BED and control subjects without BED	Phase 1 baseline (visit 0)
Secondary	Phase 1 MEQ	Difference in mean Morningness Eveningness Questionnaire scores (MEQ) between BED and control subjects without BED. MEQ score range 18 to 86, lower scores indicate more eveningness, higher scores indicate more morningness.	Phase 1 baseline (visit 0)
Secondary	Phase 1 Association between DLMO and binge eating days/week	The association between DLMO (measured in time) and binge eating days/week in BED subjects.	Phase 1 baseline (visit 0)
Secondary	Phase 2 Binge eating days/week	Differences in Binge eating days/week from baseline to endpoint between groups will be analyzed using an ANCOVA model with age as a covariate.	Phase 2 baseline (visit 0) to endpoint, on average one month.
Secondary	Phase 2 Locomotor activity acrophase	Differences in locomotor activity acrophase from baseline to endpoint between groups will be analyzed using an ANCOVA model with age as a covariate.	Phase 2 baseline (visit 0) to endpoint, on average one month.
Secondary	Phase 2 baseline (visit 0) to endpoint	Differences in MESOR (Midline Estimating Statistic of Rhythm) from baseline to endpoint between groups will be analyzed using an ANCOVA model with age as a covariate.	Phase 2 baseline (visit 0) to endpoint, on average one month.