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Microbiome-mediated Weight, Anxiety, and Stress Dysregulation in Anorexia Nervosa (Microbiome)

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ClinicalTrials.gov Identifier: NCT03119272
Recruitment Status : Recruiting
First Posted : April 18, 2017
Last Update Posted : August 9, 2019
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

Brief Summary:
The purpose of this research study is to analyze the microorganisms residing in the gut of patients with anorexia nervosa. Research has begun to link changes in the intestinal microbiota with diseases such as inflammatory bowel disease (IBS), asthma, and obesity, but although some studies have investigated the intestinal microbiota in overweight/obese individuals, very little is known about the intestinal microbiota in underweight individuals. The investigators aim to identify the enteric bacterial groups associated with adiposity, BMI, anxiety, and stress in patients with anorexia nervosa.

Condition or disease
Anorexia Nervosa

Detailed Description:

Anorexia nervosa (AN), a psychiatric disorder characterized by extreme weight dysregulation commonly presents with comorbid anxiety. Therapeutic renourishment in AN is based primarily on clinical opinion and guidelines, with a weak evidence base. Compelling data implicate the intestinal microbiota in the regulation of adiposity and behavior, providing a strong rationale for exploring the role of this complex microbial community in the emergence and maintenance of, and recovery from AN. The overarching goal is to understand the precise mechanism(s) by which intestinal bacteria contribute to dysregulation of adiposity, BMI, anxiety, and stress in patients with AN. The investigators hypothesize that intestinal microbiotas that arise from prolonged starvation contribute to increases in adiposity upon refeeding and to persistently elevated anxiety and stress in individuals with AN. To test the hypothesis the investigators propose 3 specific aims. In aim 1, the investigators will identify the enteric bacterial groups associated with adiposity, BMI, anxiety, and stress in AN patients. The investigators will characterize the intestinal microbiota in acutely low weight AN patients (T1), in the same patients following weight restoration (T2), and in healthy controls (HC) via high throughput sequencing of the 16S rRNA gene.

The investigators will compare the abundances of specific enteric taxa with adiposity, BMI and behavior (anxiety and stress) in this study population. In aim 2, The investigators will characterize the functional impact of the intestinal microbiota of AN patients on adiposity and BMI when transplanted into germ free (GF) mice. The investigators will transplant uncultured microbiotas from AN patients (at T1 and T2) and HC into GF mice and assess the impact of enteric microbes on adiposity. In aim 3, the investigators will characterize the functional impact of the intestinal microbiota of AN patients on anxiety and stress, and molecular biomarkers of these behaviors, when transplanted into GF mice. The investigators will transplant uncultured microbiotas from T1 AN patients and HC into GF mice and assess the impact of enteric microbes on anxiety and stress. GF mice gavaged with sterile phosphate buffer saline will be used as controls in aims 2 and 3. The proposed science is significant in pioneering the combination of large scale 16S rRNA gene sequencing-based studies of intestinal microbiotas in AN with exploration of their functional influence on adiposity and behavioral traits associated with AN. The results will provide direction on how best to test adjunct interventions for AN with pre-, pro-, anti-, or syn-biotics to enhance current approaches to therapeutic weight restoration and improve treatment outcome. The science is highly innovative as it will investigate an entirely novel factor in AN, the intestinal microbiota, and use a novel approach to identify enteric microbes that impact adiposity and behavior in this devastating illness. Additionally, the investigators will hope to study an entirely novel factor (namely, the intestinal microbiota) as a contributor to the underlying pathophysiology of AN.


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Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Microbiome-mediated Weight, Anxiety, and Stress Dysregulation in Anorexia Nervosa
Actual Study Start Date : April 2016
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anxiety

Group/Cohort
Anorexia Nervosa Patients
Inpatient population at Eating Disorders Unit (EDU) at the University of North Carolina Neurosciences Hospital. Recruited upon intake into the unit.
Age and Sex Matched Healthy Controls
University of North Carolina Psychiatry email listserv.



Primary Outcome Measures :
  1. Perfect total fat as it relates to each taxa (percentage abundance from phylum to the genus level) and their association with weight. [ Time Frame: 18 Months ]
    The composition and diversity of the intestinal microbiota will be characterized and correlated with adiposity. The researchers will use a DXA scan to measure this.


Secondary Outcome Measures :
  1. Anxiety level (as measured by the State-Trait Anxiety Inventory) as it relates to each taxa (percentage abundance from phylum to the genus level). [ Time Frame: 18 Months ]
    The composition and diversity of the intestinal microbiota will be characterized and correlated with anxiety measures.The enteric bacterial groups will be measured via percentage abundance from phylum to the genus level. Anxiety will be measured by the State-Trait Anxiety Inventory (STAI). The STAI questionnaire consists of 40 questions with 20 items allocated to each of the State Anxiety and Trait Anxiety subscales. The scores for each subtest range from 20 to 80, with higher scores indicating higher levels of anxiety.

  2. Stress level (as measured by the Perceived Stress Scale) as it relates to taxa (percentage abundance from phylum to the genus level). [ Time Frame: 18 Months ]
    The composition and diversity of the intestinal microbiota will be characterized and correlated with anxiety and stress measures.The enteric bacterial groups will be measured via percentage abundance from phylum to the genus level. Stress will be measured by the Perceived Stress Scale (PSS). The "Perceived Stress Scale" measures the overall level of stress. This instrument contains 10 items accessing overall appraisals of stress in the past month. The scale refers to the caregiver. Minimum score (best value)=0. Maximum score (worst value)=40. Higher values represent a worse outcome.


Biospecimen Retention:   Samples With DNA
Stool samples.


Information from the National Library of Medicine

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Ages Eligible for Study:   15 Years to 45 Years   (Child, Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
Inpatient population at Eating Disorders Unit (EDU) at UNC hospitals. Healthy controls pooled through UNC listserv.
Criteria

Inclusion Criteria:

  • Anorexia nervosa patient receiving treatment

Exclusion Criteria:

  • history of gastrointestinal tract surgery
  • history of inflammatory bowel diseases (IBD)
  • history of irritable bowel syndrome (IBS)
  • history of celiac disease
  • history of any other diagnosis that could explain chronic or recurring bowel symptoms
  • treatment in the last two months with antibiotics, non-steroid anti-inflammatory agents, or steroids.
  • eating disorders or other major psychiatric or medical issue (for healthy controls).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03119272


Contacts
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Contact: Quyen Tang, BS quyen_tang@med.unc.edu
Contact: Ian Carroll, PhD ian_carroll@med.unc.edu

Locations
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United States, North Carolina
University of North Carolina at Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Quyen Tang, BS    919-966-8231    quyen_tang@med.unc.edu   
Contact: Ian M Carroll, PHD       ian_carroll@med.unc.edu   
Sponsors and Collaborators
University of North Carolina, Chapel Hill
National Institute of Mental Health (NIMH)
Investigators
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Principal Investigator: Ian Carroll, PhD University of North Carolina

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Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT03119272     History of Changes
Other Study ID Numbers: 15-2133
1R01MH105684-01A1 ( U.S. NIH Grant/Contract )
First Posted: April 18, 2017    Key Record Dates
Last Update Posted: August 9, 2019
Last Verified: August 2019
Additional relevant MeSH terms:
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Anorexia
Anorexia Nervosa
Signs and Symptoms, Digestive
Signs and Symptoms
Feeding and Eating Disorders
Mental Disorders