Understanding the Role of Gut Microbiota in Hyperphagia in Prader-Willi Syndrome

Phase 2

Completed

Conditions: Prader-Willi Syndrome
Obesity

Interventions: Drug: NBT-NM108

Registration Number: NCT05541003

Lead Sponsor: Rutgers, The State University of New Jersey

Brief Summary: This study aims to use a high-fiber supplementation, an intervention known to create shifts in the gut microbiota towards a healthier structure, to explore the relationship between gut microbiota, appetite control and feeding behavior in PWS patients.

Detailed Description: This study is recruiting PWS patients aged 18-35 years who have not received growth hormone treatment in the previous 6 months. Study candidates will be recruited from Robert Wood Johnson. Participants will attend a baseline visit at the Center for Advanced Human Brain Imaging Research (CAHBIR) at Rutgers University, during which functional magnetic resonance imaging (fMRI) coupled with a meal test will be performed to assess peripheral and central feeding pathways (7, 8). fMRI scans will be performed during resting state to assess functional connectivity of feeding related networks, with a specific focus on connectivity between the hypothalamus, insula, anterior cingulate, ventromedial/orbitofrontal prefrontal cortex and amygdala (9, 10). Activation to food (vs non-food) images will be assessed to index responsivity to appetitive feeding networks including the above regions and the ventral striatum using paradigms that have previously been found to be sensitive to trait and state in multiple studies (11-13). Thereafter participants will consume a liquid meal (525 kcal; Ensure Plus, Abbott). fMRI will be repeated immediately after the meal. Participants will obtain laboratory work coupled with a meal test to assess satiety hormones and inflammatory markers. Fasting blood draw will be taken, and the participants will consume a liquid meal (525 kcal; Ensure Plus, Abbot) followed by blood draws at 30, 60, 120, 180 and 240 min post-meal. Upon completion of baseline testing and providing a fecal sample, participants will consume NBT-NM108 (a mixture of inulin, Fibersol-2, and brans of oat, wheat, corn and sorghum; Notitia Biotechnologies) daily for 4 weeks. At the completion of the 4-week intervention, all sampling and testing will be repeated as per baseline. At baseline and end of intervention, participants will be interviewed with appetite and physical activity questionnaires (Appendix C and G) and requested to complete a 24-h food recall using MyFitnessPal, a mobile health app on their phone.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 12

Inclusion Criteria

Aged between 18-35 (inclusive)
Confirmed PWS with genetic testing
No growth hormone treatment in the previous 6 months
Body weight < 300 lbs.

Exclusion Criteria

History of other gastrointestinal disorders such as small intestinal bacterial overgrowth, celiac disease, inflammatory bowel disease, or irritable bowel syndrome.
Pregnancy or breastfeeding
Prior gastrointestinal or bariatric surgery
Immunocompromised e.g., cancer treatment, bone marrow/organ transplant, immune deficiency, poorly controlled HIV/AIDS, prolonged use of steroids or other immunosuppressant medications
Antibiotic administration in the previous 30 days
Participation in other weight-loss programs in the previous 3 months.
Administration of pre/probiotic supplements or antibiotics.
Growth hormone administration in the previous 6 months
Must have access to a smartphone, tablet, computer, or other qualifying internet-enabled device and be able to follow instructions.
Individuals who are not proficient in English
Contraindications for MRI scanning, including Ferrous material implanted in or on the body, including flakes or filings, surgical clips, bullets, or electrical devices such as a pacemaker, or nonremovable ferrous jewelry (fillings in teeth and permanent retainers are permitted). Individuals with surgical pins or plates above the neck are excluded. Surgical pins or plates below the neck are exclusions, except when the material is fixed to bone, and considered acceptable by the Reference Manual for Magnetic Resonance Safety. Implants and Devices, 2020 Edition. Almost all recent orthopedic implants are made of materials that are not ferromagnetic and therefore are safe for scanning, and even though some screws are still made of ferromagnetic materials these are firmly screwed into bone. In cases where the material is unknown or deemed unsafe for scanning by the Reference Manual for Magnetic Resonance Safety. Implants and Devices, the participant will be excluded. History of eye injury involving metallic materials, shavings in eyes, or welding without a face mask. Lead/iron tattoos and tattoos performed by a nonprofessional artist if the pigment material is unknown. Claustrophobia (history of significant anxiety in closed places).
Back problem that would prevent the subject from laying still comfortably for up to 60 minutes.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental Arm	NBT-NM108	All participants will receive NBT-NM108 prepared as muffin (each contains 30 g of the product) for 4 weeks. The dosage will be 2 muffins a day. This dosage of NBT-NM108 will provide 24 g/day of dietary fibers.

Primary Outcome Measures

Name	Time	Method
Microbiome Analysis: Beta Diversity	Week 4	The Bray-Curtis distance was used to compute the distances for each sample. Bray-Curtis distance uses species abundance information and membership to calculate the distance between samples. The Bray-Curtis dissimilarity index for a sample ranges between 0 and 1. A value of 0 indicates no difference between the samples, while a value of 1 represents the maximum distance between them
Microbiome Analysis: Alpha Diversity	Week 4	Alpha diversity measured by Shannon index. "The Shannon Index is a measure of diversity of microbial species that takes into account both abundance (the number of species present) and evenness (how close the numbers for each species are). The Shannon index can be calculated using the following equation: H= -∑(i=1)\^s pi ln(pi). A value of zero for H indicates that a community has only one species. The higher the value of H, the higher the diversity of species in a particular community.

Secondary Outcome Measures

Name	Time	Method
Calorie Count	Week 4	24 hour dietary recall recorded in MyFitnessPal application measured in kcal.
Acyl-Ghrelin Level	Week 4	Early response to meal post-intervention is 0-30min. Late response phase to meal post-intervention is 60-180min.
Glucagon Like Peptide 1 (GLP1)	Week 4	GLP1 levels were measured in patients after fiber intervention. Early response to meal post-intervention is 0-30min. Late response phase to meal post-intervention is 60-180min.
Glucose Level	Week 4	Glucose levels were measured in patients after fiber intervention. Early phase (0-30min) and late phase response (60-180min) to a mixed meal tolerance test was collected.
Weight	Week 4	Weight in kg
Insulin Level	Week 4	Insulin levels were measured in patients after fiber intervention. Early response to meal post-intervention is 0-30min. Late response phase to meal post-intervention is 60-180min.
Peptide YY (PYY)	Week 4	Early response to meal post-intervention is 0-30min. Late response phase to meal post-intervention is 60-180min.
Hyperphagia Questionnaire	Week 4	Appetite behavior measured by questionnaire measured by likert scale. The scores should improve from week 0 to week 4. Higher scores indicate worse hyperphagia. The questionnaire includes 11 questions measured on a 5-point Likert scale, which are summarized in a total hyperphagia score (range: 11-55). Three subscores were summed: hyperphagic behavior (range: 5-25), hyperphagic drive (range: 4-20) and hyperphagic severity (range: 2-10). The scores should improve from week 0 to week 4 with intervention. Higher scores indicate worse hyperphagia.