Fiber Intervention on Gut Microbiota in Children With Prader-Willi Syndrome

NCT04150991 | Completed

• 1 other identifier: Pro00069477
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

Prader-Willi syndrome (PWS) is the most common syndromic cause of obesity. Individuals with PWS characteristically experience excessive weight gain and severe hyperphagia with food compulsivity in early childhood, which often leads to the onset of obesity and metabolic complications. The pathogenesis of hyperphagia and progressive weight gain in PWS is far from being understood, and thus efficacious interventions are still under development. Emerging evidence indicates an important etiological contribution of dysbiotic gut microbiota in the hyperphagia, obesity and metabolic abnormalities associated with PWS, implicating a potentially effective target for appetite control and alleviation of obesity in PWS. This study aims to evaluate whether dietary fibers can improve hyperphagia and metabolic profile in children with PWS, and further will determine if these improvements correlate with dietary-fiber-induced changes of the gut microbiota. Twenty children with PWS (age 5-17 years) will receive 3-week fiber or placebo treatment and 3-week alternate treatment with a 4-week washout period in between. A validated PWS-specific hyperphagia questionnaire will be used to assess the severity of hyperphagia in participants. Fasting blood and fecal samples will be collected for the analyses of appetite-related hormones, metabolic biomarkers, bacterial composition and gut metabolites. This study should provide potential new approaches for effective non-pharmacologic treatment of excessive weight gain and hyperphagia associated with PWS to improve overall health and quality of life in affected patients.

Conditions

Prader-Willi Syndrome; Hyperphagia

Keywords

Fiber; Gut microbiome; Hyperphagia; Prader-Willi Syndrome

Outcome Measures

Primary Outcomes (1)

• Changes in hyperphagia

  Change in hyperphagia will be measured by the Hyperphagia Questionnaire for Clinical Trials. This questionnaire consists of nine items with responses ranging from 0-4 units each (possible total score range: 0-36; higher scores indicate higher degree of hyperphagia; reductions in score from baseline indicate improvement in hyperphagia-related behaviors).

  Week 1, 3, 7 &10

Secondary Outcomes (6)

• Changes in gut microbiota

  Week 1, 3, 7 &10

• Changes in appetite and satiety hormones

  Week 1, 3, 7 &10

• Changes in inflammatory status

  Week 1, 3, 7 &10

• Changes in metabolic markers

  Week 1, 3, 7 &10

• Changes in metabolomics

  Week 1, 3, 7 &10

Study Arms (2)

Fiber intervention

EXPERIMENTAL

The investigator's targeted supplemental fiber mixture (35 g total) will be composed of 6g of fiber from oligofructose + 10g from resistant maltodextrin + 12g from acacia gum + 4g from whole foods + 3g from RS2; and will be split into three meals each day.

Other: Fiber intervention

Placebo treatment

PLACEBO COMPARATOR

Maltodextrin will be used as a placebo control, as it is digested in the small intestine and thus does not exert local effects in the colon.

Other: Placebo treatment

Interventions

Fiber intervention OTHER

Each subject will supplement his/her normal dietary intake with 35 grams of dietary fiber daily for three consecutive weeks.

Fiber intervention

Placebo treatment OTHER

Each subject will supplement his/her normal dietary intake with an 18.53-g maltodextrin placebo daily for three consecutive weeks.

Placebo treatment

Eligibility Criteria

• Age: 5 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• PWS diagnosis confirmed by chromosome analysis;
• Age 5-25 years;
• Informed consent/ assent and willingness to comply with study procedures;
• Free T4, TSH values in the normal range (either endogenous or with thyroxine replacement);
• Weight stable (Body Mass Index \[BMI\] percentile fluctuation \< 5%) over the preceding 2 months;
• Stable growth hormone dose over the prior 6 months.

You may not qualify if:

• Other clinically significant diseases including diabetes mellitus, chronic inflammatory bowel disease, chronic severe liver, kidney disease or neurologic disorders;
• Concomitant use of medication/investigational drug known to affect body weight in the past year;
• Antibiotic use in the past 60 days;
• Probiotic and/or prebiotic supplements use in the past 30 days.

Sponsors & Collaborators

• University of Alberta: lead

Study Sites (1)

Li Ka Shing Centre for Health Research Innovation

Edmonton, Alberta, T6G 2E1, Canada

Location

Related Publications (3)

• Irizarry KA, Miller M, Freemark M, Haqq AM. Prader Willi Syndrome: Genetics, Metabolomics, Hormonal Function, and New Approaches to Therapy. Adv Pediatr. 2016 Aug;63(1):47-77. doi: 10.1016/j.yapd.2016.04.005. No abstract available.

  PMID: 27426895 BACKGROUND

• Irizarry KA, Bain J, Butler MG, Ilkayeva O, Muehlbauer M, Haqq AM, Freemark M. Metabolic profiling in Prader-Willi syndrome and nonsyndromic obesity: sex differences and the role of growth hormone. Clin Endocrinol (Oxf). 2015 Dec;83(6):797-805. doi: 10.1111/cen.12766. Epub 2015 Apr 1.

  PMID: 25736874 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

MeSH Terms

Conditions

Prader-Willi Syndrome; Hyperphagia

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; Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Andrea Haqq, MD, MHS

  University of Alberta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will receive 3-week fiber/placebo treatment and 3-week alternate fiber/placebo treatment with a 4-week washout period in between.

Study Record Dates

• First Submitted: October 15, 2019
• First Posted: November 5, 2019
• Study Start: July 1, 2019
• Primary Completion: February 22, 2023
• Study Completion: February 22, 2023
• Last Updated: April 18, 2023

Record last verified: 2023-04

Locations

CA (1)