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
|Condition or disease|
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.
|Study Type :||Observational|
|Estimated Enrollment :||200 participants|
|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|
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.
- 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.
- 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.
- 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
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03119272
|Contact: Quyen Tang, BSemail@example.com|
|Contact: Ian Carroll, PhDfirstname.lastname@example.org|
|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 email@example.com|
|Contact: Ian M Carroll, PHD firstname.lastname@example.org|
|Principal Investigator:||Ian Carroll, PhD||University of North Carolina|