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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Prader-Willi Syndrome, Obesity

Intervention / Treatment
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* Drug: NBT-NM108


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Arm<br>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. | Drug: NBT-NM108<br>* All patients will consume NBT-NM108 in the form of 2 muffins daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gut microbiota composition | Network analysis will be employed to identify guild-level structure in the gut microbiota. When supplemented with dietary fiber, gut bacteria exhibited co-abundance patterns and formed genome interaction groups (GIGs) or guilds (an ecological group in which members exploit an environmental resource in a similar way and show co-abundant behavior). | Weeks 0 | 
| Gut microbiota composition | Network analysis will be employed to identify guild-level structure in the gut microbiota. When supplemented with dietary fiber, gut bacteria exhibited co-abundance patterns and formed genome interaction groups (GIGs) or guilds (an ecological group in which members exploit an environmental resource in a similar way and show co-abundant behavior). | Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight | Weight in lbs | Week 0 | 
| Weight | Weight in lbs | Week 1 | 
| Weight | Weight in lbs | Week 2 | 
| Weight | Weight in lbs | Week 3 | 
| Weight | Weight in lbs | Week 4 | 
| Ghrelin level | fasting and post-prandial hormone level measured in mg/dl | Week 0 and week 4 | 
| Ghrelin level | fasting and post-prandial hormone level measured in mg/dl | Week 4 | 
| Insulin level | fasting and post-prandial hormone level measured in mg/dl | Week 0 and week 4 | 
| Insulin level | fasting and post-prandial hormone level measured in mg/dl | Week 4 | 
| Glucose level | fasting and post-prandial hormone level measured in mg/dl | Week 0 and week 4 | 
| Glucose level | fasting and post-prandial hormone level measured in mg/dl | Week 4 | 
| Functional MRI | functional MRI in the resting state and post-prandial 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. The output is an image of brain activation. | Week 0 | 
| Functional MRI | functional MRI in the resting state and post-prandial 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. The output is an image of brain activation. | Week 4 | 
| 24 hour dietary recall | 24 hour dietary recall recorded in MyFitnessPal application measured in kcal. It is anticipated that the calorie count decreases from week 0 to week 4. | Week 0 and week 4 | 
| 24 hour dietary recall | 24 hour dietary recall recorded in MyFitnessPal application measured in kcal. It is anticipated that the calorie count decreases from week 0 to week 4. | Week 4 | 
| Hyperphagia questionnaire | Appetite behavior measured by questionnaire measured by likert scale. The scores should improve from week 0 to week 4. Higher scores indicate worse hyperphagia. Lowest score is 13 and highest score is 65. | Week 0 and week 4 | 
| Hyperphagia questionnaire | Appetite behavior measured by questionnaire measured by likert scale. The scores should improve from week 0 to week 4. Higher scores indicate worse hyperphagia. Lowest score is 13 and highest score is 65. | Week 4 |