Clinical trial NCT05541003: Understanding the Role of Gut Microbiota in Hyperphagia in Prader-Willi Syndrome
Official title: Understanding the Role of Gut Microbiota in Hyperphagia in Prader-Willi Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prader-Willi Syndrome
Obesity
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
First posted: 2022-09-15
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Microbiome Analysis: Alpha Diversity
timeFrame: Weeks 0
measure: Microbiome Analysis: Alpha Diversity
timeFrame: Week 4
measure: Microbiome Analysis: Beta Diversity
timeFrame: Week 0
measure: Microbiome Analysis: Beta Diversity
timeFrame: Week 4
Secondary outcomes:
measure: Weight
timeFrame: Week 4
measure: Acyl-Ghrelin Level
timeFrame: Week 0
measure: Acyl-Ghrelin Level
timeFrame: Week 4
measure: Peptide YY (PYY)
timeFrame: Week 0
measure: Peptide YY (PYY)
timeFrame: Week 4
measure: Glucagon Like Peptide 1 (GLP1)
timeFrame: Week 0
measure: Glucagon Like Peptide 1 (GLP1)
timeFrame: Week 4
measure: Insulin Level
timeFrame: Week 0
measure: Insulin Level
timeFrame: Week 4
measure: Glucose Level
timeFrame: Week 0
measure: Glucose Level
timeFrame: Week 4
measure: Calorie Count
timeFrame: Week 0
measure: Calorie Count
timeFrame: Week 4
measure: Hyperphagia Questionnaire
timeFrame: Week 0
measure: Hyperphagia Questionnaire
timeFrame: Week 4
Other outcomes:
Locations:
city: New Brunswick
country: United States
facility: Robert Wood Johnson University Hospital
state: New Jersey
Study officials:
References:
citation: Holland AJ, Treasure J, Coskeran P, Dallow J, Milton N, Hillhouse E. Measurement of excessive appetite and metabolic changes in Prader-Willi syndrome. Int J Obes Relat Metab Disord. 1993 Sep;17(9):527-32.
citation: Fieldstone A, Zipf WB, Sarter MF, Berntson GG. Food intake in Prader-Willi syndrome and controls with obesity after administration of a benzodiazepine receptor agonist. Obes Res. 1998 Jan;6(1):29-33. doi: 10.1002/j.1550-8528.1998.tb00311.x.
citation: Proffitt J, Osann K, McManus B, Kimonis VE, Heinemann J, Butler MG, Stevenson DA, Gold JA. Contributing factors of mortality in Prader-Willi syndrome. Am J Med Genet A. 2019 Feb;179(2):196-205. doi: 10.1002/ajmg.a.60688. Epub 2018 Dec 19.
citation: Martinez Michel L, Haqq AM, Wismer WV. A review of chemosensory perceptions, food preferences and food-related behaviours in subjects with Prader-Willi Syndrome. Appetite. 2016 Apr 1;99:17-24. doi: 10.1016/j.appet.2015.12.021. Epub 2015 Dec 20.
citation: Zhang C, Yin A, Li H, Wang R, Wu G, Shen J, Zhang M, Wang L, Hou Y, Ouyang H, Zhang Y, Zheng Y, Wang J, Lv X, Wang Y, Zhang F, Zeng B, Li W, Yan F, Zhao Y, Pang X, Zhang X, Fu H, Chen F, Zhao N, Hamaker BR, Bridgewater LC, Weinkove D, Clement K, Dore J, Holmes E, Xiao H, Zhao G, Yang S, Bork P, Nicholson JK, Wei H, Tang H, Zhang X, Zhao L. Dietary Modulation of Gut Microbiota Contributes to Alleviation of Both Genetic and Simple Obesity in Children. EBioMedicine. 2015 Jul 10;2(8):968-84. doi: 10.1016/j.ebiom.2015.07.007. eCollection 2015 Aug.
citation: Purtell L, Sze L, Loughnan G, Smith E, Herzog H, Sainsbury A, Steinbeck K, Campbell LV, Viardot A. In adults with Prader-Willi syndrome, elevated ghrelin levels are more consistent with hyperphagia than high PYY and GLP-1 levels. Neuropeptides. 2011 Aug;45(4):301-7. doi: 10.1016/j.npep.2011.06.001. Epub 2011 Jul 1.
citation: Dykens EM, Maxwell MA, Pantino E, Kossler R, Roof E. Assessment of hyperphagia in Prader-Willi syndrome. Obesity (Silver Spring). 2007 Jul;15(7):1816-26. doi: 10.1038/oby.2007.216.