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Prader-Willi SyndromeNCT04150991

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

A study testing Fiber intervention in people with Prader-Willi Syndrome and Hyperphagia, run by University of Alberta at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 5 to 25 years
Conditions the study is for
Prader-Willi Syndrome, Hyperphagia
What is being tested?
Fiber intervention
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
14 participants
Where
1 siteCanada
Study dates
1 Jul 2019to 22 Feb 2023
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 5 to 25 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

Canada1 site
  • Li Ka Shing Centre for Health Research Innovation

    Edmonton, Alberta, T6G 2E1

Other trials in Canada

About this study

Official title: Profiling of the Gut Microbiome in Children With Prader-Willi Syndrome: a Fiber Intervention to Target Hyperphagia (AIM 2)

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.

Read the detailed description

Background: 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 development 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 being developed. Emerging evidence indicates an important etiological contribution of dysbiotic gut microbiota to the hyperphagia, obesity and metabolic abnormalities associated with PWS, implicating a potentially effective target for appetite control and alleviation of obesity in PWS. The therapeutic potential of manipulating gut microbiota through diet has been scarcely assessed in PWS; more comprehensive evaluations are greatly needed.

Specific objectives: 1) to assess the effects of a 3-week dietary fiber intervention on gut microbiota, hyperphagia, and metabolic profile in children with PWS; 2) to determine whether changes in gut microbial composition and function correlate with changes in the degree of hyperphagia, metabolic hormones, insulin sensitivity, inflammatory markers, and metabolites implicated in cardiometabolic diseases.

Methodological Approach: In a cross-sectional design, 20 children with PWS aged 5 to 17 years will be recruited from the Stollery Children's Hospital, Edmonton. Eligible participants will have normal values of free thyroxine and thyroid-stimulating hormone (either endogenous or with thyroxine replacement) as well as stable body weight and growth hormone dose. Children with other clinically significant disease (diabetes mellitus, chronic inflammatory bowel disease, chronic severe liver or kidney disease), or recent use of medications known to affect body weight and gut microbiota (investigational drugs, antibiotics, prebiotic and/or probiotic supplements) will be excluded. Participants will be randomly assigned to consume either 35 g supplemental fiber mixture/d (oligofructose, resistant maltodextrin, acacia gum, whole foods, and resistant starch type II) or an equicaloric dose of a 17.6-g maltodextrin placebo/d (GLOBE® Plus 10 DE Maltodextrin 100200; Ingredion) for 3 wk. This will be followed by a 4-wk washout period and an alternate treatment for another 3 wk. Fecal samples will be collected to analyze gut microbiota composition (using 16S ribosomal ribonucleic acid [rRNA] tag sequencing) and function (metabolites produced by microbiota: SCFAs and bile acids). Microbiota composition will be characterized at phylum to genus level, and sequences will be clustered to Operational Taxonomic Units to calculate alpha-diversity (by Shannon index). Fasting blood samples will be used to measure appetite-related hormones, and metabolic and inflammatory markers. A validated PWS-specific hyperphagia questionnaire will be used to assess participants' food-related behaviors. A 3-day dietary record including physical activity questions will be administered for the assessment of macro- and-micronutrient intake and diet quality as well as physical activity level of the participants. In addition, anthropometric data (body weight, height and waist circumference [WC]) will be obtained to track changes.

Outcomes: 1) Primary outcome: Change in hyperphagia score; 2) Secondary outcomes: Changes in: a. Fecal microbial composition and function; b. Hormones (acylated ghrelin, PYY, GLP-1, adiponectin and leptin; c. Metabolic and inflammatory markers (glucose, insulin, lipids, AST, ALT, hs-CRP); d. Metabolomics profile (amino acids, branched chain keto acids, acylcarnitines, ceramides, TMAO, choline and betaine); and e. body weight, height and WC.

Deliverables: 1) the feasibility of using a fiber intervention to reduce hyperphagia and improve metabolism and inflammation via beneficial changes in the microbiota in children with PWS; 2) the particular microbial composition and functional profiles associated with metabolic improvement and/or weight loss can aid in the future development of microbial-targeted prebiotic therapies. Results from this study will be used to guide the design of effective treatment strategies to reduce hyperphagia and improve metabolic health in children with PWS.

Being tested
Fiber intervention, Placebo treatment
Keywords
Fiber, Gut microbiome, Hyperphagia, Prader-Willi Syndrome
Medical subject headings
Prader-Willi Syndrome, Hyperphagia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Fiber interventionOther

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

  • Placebo treatmentOther

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

Study groups in NCT04150991
Study groupRoleWhat they receive
Fiber interventionExperimentalThe 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.
Receives: Other: Fiber intervention
Placebo treatmentPlacebo comparatorMaltodextrin 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.
Receives: Other: Placebo treatment

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: Week 1, 3, 7 &10

Secondary outcomes (6)
  1. Changes in gut microbiota

    16SrRNA-sequencing and whole metagenome sequencing will performed to determine gut microbial community changes induced by dietary fibers.

    Measured: Week 1, 3, 7 &10

  2. Changes in appetite and satiety hormones

    Fasting blood samples will be collected to quantify the plasma concentrations of circulating appetite regulating hormones.

    Measured: Week 1, 3, 7 &10

  3. Changes in inflammatory status

    Plasma levels of C-Reactive Protein (mg/L) will be measured to determine if fiber intervention can improve inflammatory outcomes.

    Measured: Week 1, 3, 7 &10

  4. Changes in metabolic markers

    Plasma levels of metabolic markers will be measured determine if fiber intervention can improve metabolic functions.

    Measured: Week 1, 3, 7 &10

  5. Changes in metabolomics

    Plasma levels of metabolomics will be measured determine if fiber intervention can improve metabolic functions.

    Measured: Week 1, 3, 7 &10

  6. Change in anthropometric measurements

    Weight will be measured to the nearest 0.1kg using a calibrated scale. Height will be measured to the nearest 0.1cm using a wall-mounted stadiometer. Waist circumference will be measured to the nearest 0.1 cm at the top of the iliac crest using an inelastic measuring tape. Weight and height will be combined to report BMI in kg/m^2.

    Measured: Week 1, 3, 7 &10

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Nov 2019
  2. Study start1 Jul 2019
  3. Primary completion22 Feb 2023
  4. Study completion22 Feb 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Model description
Participants will receive 3-week fiber/placebo treatment and 3-week alternate fiber/placebo treatment with a 4-week washout period in between.
Masking
Single blind
Who is masked
Participant
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04150991
Sponsor's protocol ID
Pro00069477
Status last verified
Apr 2023
First submitted
15 Oct 2019
Last updated
18 Apr 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 27426895
  • 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.

    PubMed 25736874
  • 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.

    PubMed 26425705

Questions about this trial

What is this clinical trial studying?

A study testing Fiber intervention in people with Prader-Willi Syndrome and Hyperphagia, run by University of Alberta at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes in hyperphagia (time frame: Week 1, 3, 7 &10). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04150991, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2023.

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