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

NCT05541003 | Completed Phase 2 Results FDA Drug

• 1 other identifier: Pro2022000828
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Prader-Willi Syndrome; Obesity

Outcome Measures

Primary Outcomes (4)

• Microbiome Analysis: Alpha Diversity

  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.

  Weeks 0

• Microbiome Analysis: Alpha Diversity

  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.

  Week 4

• Microbiome Analysis: Beta Diversity

  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

  Week 0

• Microbiome Analysis: Beta Diversity

  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

  Week 4

Secondary Outcomes (15)

• Weight

  Week 4

• Acyl-Ghrelin Level

  Week 0

• Acyl-Ghrelin Level

  Week 4

• Peptide YY (PYY)

  Week 0

• Peptide YY (PYY)

  Week 4

Study Arms (1)

Experimental Arm

EXPERIMENTAL

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

Interventions

NBT-NM108 DRUG

All patients will consume NBT-NM108 in the form of 2 muffins daily.

Experimental Arm

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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
• Back problem that would prevent the subject from laying still comfortably for up to 60 minutes.

Sponsors & Collaborators

• Rutgers, The State University of New Jersey: lead

Study Sites (1)

Robert Wood Johnson University Hospital

New Brunswick, New Jersey, 08901, United States

Location

Related Publications (7)

• 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.

  PMID: 8220655 BACKGROUND

• 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.

  PMID: 9526967 BACKGROUND

• 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.

  PMID: 30569567 BACKGROUND

• 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.

  PMID: 26713776 BACKGROUND

• 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.

  PMID: 26425705 BACKGROUND

• 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.

  PMID: 21722955 BACKGROUND

• 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.

  PMID: 17636101 BACKGROUND

MeSH Terms

Conditions

Prader-Willi Syndrome; Obesity

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Imprinting Disorders; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

There was a variance in BMI in patients accepted. We anticipate this led the varied difference in response in data. Additionally, two of the patients had PWS while the remainder of patients had non-genetic obesity. We anticipate this also led to the varied difference in response in data.

Results Point of Contact

• Title: Dr. Keerthana Kesavarapu
• Organization: Robert Wood Johnson

kk1132@rwjms.rutgers.edu

6784690425

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 1, 2022
• First Posted: September 15, 2022
• Study Start: January 6, 2023
• Primary Completion: May 29, 2023
• Study Completion: May 30, 2023
• Last Updated: July 16, 2024
• Results First Posted: July 16, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)