Homeostatic and Non-homeostatic Processing of Food Cues in Anorexia Nervosa

• ClinicalTrials.gov Identifier: NCT03075371
• Recruitment Status: Completed
• First Posted: March 9, 2017
• Last Update Posted: October 3, 2019
• Sponsor: University of Heidelberg Medical Center
• Collaborator: German Research Foundation
• Information provided by (Responsible Party): Joe Simon, University of Heidelberg Medical Center

Study Description

Brief Summary:

The goal of the present study is to investigate metabolic gut-brain signaling and the neural correlates of distraction from visual food cues in patients with Anorexia nervosa and healthy controls.

Condition or disease	Intervention/treatment	Phase
Anorexia Nervosa; Healthy	Other: Glucose; Other: Placebo	Not Applicable

Detailed Description:

Anorexia nervosa (AN) is an eating disorder with high morbidity and lifetime mortality. This eating disorder is mainly characterized by restricted food intake despite a severely low body weight. Given the pronounced self-starvation in AN, the investigation of homeostatic food processing, and its interaction with the reward system is of great scientific interest. Previous research in AN patients has almost exclusively focused on cortical, non-homeostatic (e.g., reward related) food processing. Therefore, the primary aim of the present study is to investigate metabolic gut-brain signaling by focusing on the responsivity of the hypothalamus (i.e., the core region of homeostatic control) and the mesocorticolimbic reward system. A secondary aim is to study the interaction between the mesocorticolimbic reward system and the homeostatic (i.e., hypothalamus) system. Metabolic gut-brain signaling will be assessed by applying a single-blind, randomized, crossover design of intragastric infusion of glucose or water. This approach allows the study of gut-brain signaling to the hypothalamus and the reward system by controlling for sensory aspects of food intake (sight, smell, and taste) in AN patients and healthy controls. Furthermore, we will measure how cognitive strategies to control the desire for visual food cues (top-down control) affect the mesocorticolimbic and hypothalamic systems in AN patients differently than in healthy controls. The interaction between the hypothalamus and the mesocorticolimbic reward system will be investigated using an effective connectivity analysis. Functional magnetic resonance imaging with high spatial resolution and with an optimized protocol for the investigation of the hypothalamus and the mesocorticolimbic reward system will be used to study for the first time homeostatic and non-homeostatic food cue processing in AN patients.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 85 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Basic Science
• Official Title: Homeostatic and Non-homeostatic Processing of Food Cues in Anorexia Nervosa
• Actual Study Start Date: September 2014
• Actual Primary Completion Date: December 2018
• Actual Study Completion Date: February 2019

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: intragastric glucose administration	Other: Glucose; 75 g of glucose dissolved in 300 ml of water
Placebo Comparator: intragastric water administration	Other: Placebo; 300 ml of tap water

Outcome Measures

Primary Outcome Measures :

1. Resting state brain activity using fMRI [ Time Frame: 35 min ]
   Functional brain imaging will be employed to assess metabolic gut-brain signaling during a single blind, randomized cross-over design of gastric glucose vs. water infusion.
2. Experimental fMRI task [ Time Frame: 20 min ]
   Participants will be asked to either view food or nonfood images or to down-regulate their emotional response by distracting themselves from the stimuli by solving an arithmetic task.

Secondary Outcome Measures :

1. Analysis of hormonal satiety signaling [ Time Frame: 30 min before scanning, 30 min after intragastric feeding, 60 min after intragastric feeding ]
   Blood is collected for the measurement of peripheral ghrelin. In total, three blood samples will be collected.
2. Self-report questionnaire regarding eating behavior (Dutch Eating Behavior Questionnaire) [ Time Frame: 30 min ]
   Psychometric tests will be employed to assess eating behavior and eating disorder psychopathology (using the Dutch Eating Behavior Questionnaire).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• patients that meet the diagnostic criteria for AN (DSM-V criteria)
• Medically stable patients with a BMI < 17.5 kg/m² and > 13 kg/m²; Healthy controls with a BMI <25 kg/m² and >18.5 kg/m²
• Over Age of 18 years
• no other lifetimes or current medical illness that could potentially affect appetite or body weight
• right-handedness
• normal or corrected-to-normal vision

Exclusion Criteria:

• history of head injury or surgery
• history of neurological disorder
• severe psychiatric comorbidity (psychosis, bipolar disorder, substance abuse)
• smoking
• borderline personality disorder
• current psychotropic medication
• inability to undergo fMRI scanning (e.g. metallic implants, claustrophobia, Pacemakers)
• pregnancy

Contacts and Locations

Locations

Germany

University Hospital Heidelberg

Heidelberg, Germany

Sponsors and Collaborators

University of Heidelberg Medical Center

German Research Foundation

Investigators

• Principal Investigator: Joe Simon, Dr. Dipl. Psych.; University Hospital Heidelberg

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Stopyra MA, Friederich HC, Lavandier N, Mönning E, Bendszus M, Herzog W, Simon JJ. Homeostasis and food craving in obesity: a functional MRI study. Int J Obes (Lond). 2021 Nov;45(11):2464-2470. doi: 10.1038/s41366-021-00920-4. Epub 2021 Aug 17.

Stopyra MA, Friederich HC, Mönning E, Lavandier N, Bendszus M, Herzog W, Simon JJ. The influence of homeostatic mechanisms on neural regulation of food craving in anorexia nervosa. Psychol Med. 2021 Apr;51(6):1011-1019. doi: 10.1017/S0033291719003970. Epub 2020 Jan 14.

Stopyra MA, Friederich HC, Sailer S, Pauen S, Bendszus M, Herzog W, Simon JJ. The effect of intestinal glucose load on neural regulation of food craving. Nutr Neurosci. 2021 Feb;24(2):109-118. doi: 10.1080/1028415X.2019.1600275. Epub 2019 Apr 15.

• Responsible Party: Joe Simon, Principal Investigator, University of Heidelberg Medical Center
• ClinicalTrials.gov Identifier: NCT03075371
• Other Study ID Numbers: UHeidelbergMedCtr
• First Posted: March 9, 2017
• Last Update Posted: October 3, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Anorexia; Anorexia Nervosa; Signs and Symptoms, Digestive; Feeding and Eating Disorders; Mental Disorders