Trial Outcomes & Findings for Understanding the Role of Gut Microbiota in Hyperphagia in Prader-Willi Syndrome (NCT NCT05541003)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

12 participants

Primary outcome timeframe

Weeks 0

Results posted on

2024-07-16

Participant Flow

Recruitment time period was from 11/1/2022 to 3/1/2023. Recruitment occurred from Robert Wood Johnson medical clinics.

No patients were excluded from the study before assignment to arms or groups.

Participant milestones

Participant milestones
Measure	Experimental Arm 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. NBT-NM108: All patients will consume NBT-NM108 in the form of 2 muffins daily.
Overall Study STARTED	12
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Fiber Intervention n=12 Participants All patients were given 48 grams of NBT-NM108 dietary fiber in the form of 2 muffins per day
Age, Continuous	28 Years STANDARD_DEVIATION 9 • n=12 Participants
Sex: Female, Male Female	9 Participants n=12 Participants
Sex: Female, Male Male	3 Participants n=12 Participants
Region of Enrollment United States	12 Participants n=12 Participants
Weight	107.01 kilogram STANDARD_DEVIATION 21.33 • n=12 Participants
BMI	38.58 kg/m^2 STANDARD_DEVIATION 7.82 • n=12 Participants
Systolic Blood Pressure	135 mmHg STANDARD_DEVIATION 13.64 • n=12 Participants
Diastolic Blood Pressure	88.91 mmHg STANDARD_DEVIATION 9.63 • n=12 Participants
Heart Rate	81.55 Beats per minute STANDARD_DEVIATION 15.92 • n=12 Participants

PRIMARY outcome

Timeframe: Weeks 0

Population: 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. No units.

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.

Outcome measures

Outcome measures
Measure	Microbiome Structure n=10 Participants In this pilot study, we collected 20 fecal samples from 10 subjects before and after the dietary intervention. We extracted the metagenomic DNA from the fecal samples and applied 16S rRNA gene amplicon sequencing to understand the impact of NBT-NM108 on the gut microbiome. We obtained \~980,000 high-quality sequencing reads from 20 samples and have identified 757 amplicon sequence variants (ASVs) from these samples. For subsequent analysis the number of sequencing reads per sample was normalized to 34,000 per sample. Alpha and beta diversity were analyzed to assess changes of the overall gut microbiota structure. Alpha diversity describes the overall gut microbiota structure within a single sample.
Microbiome Analysis: Alpha Diversity	4.89 Shannon index Standard Deviation 0.46

PRIMARY outcome

Timeframe: Week 4

Population: For alpha diversity, Shannon index was used.

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.

Outcome measures

Outcome measures
Measure	Microbiome Structure n=10 Participants In this pilot study, we collected 20 fecal samples from 10 subjects before and after the dietary intervention. We extracted the metagenomic DNA from the fecal samples and applied 16S rRNA gene amplicon sequencing to understand the impact of NBT-NM108 on the gut microbiome. We obtained \~980,000 high-quality sequencing reads from 20 samples and have identified 757 amplicon sequence variants (ASVs) from these samples. For subsequent analysis the number of sequencing reads per sample was normalized to 34,000 per sample. Alpha and beta diversity were analyzed to assess changes of the overall gut microbiota structure. Alpha diversity describes the overall gut microbiota structure within a single sample.
Microbiome Analysis: Alpha Diversity	4.73 Shannon index Standard Deviation 0.41

PRIMARY outcome

Timeframe: Week 0

Population: For beta diversity, Bray-Curtis dissimilarity index was computed for each sample. Bray-Curtis dissimilarity index is represented as Median (Inter-Quartile Range).

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

Outcome measures

Outcome measures
Measure	Microbiome Structure n=10 Participants In this pilot study, we collected 20 fecal samples from 10 subjects before and after the dietary intervention. We extracted the metagenomic DNA from the fecal samples and applied 16S rRNA gene amplicon sequencing to understand the impact of NBT-NM108 on the gut microbiome. We obtained \~980,000 high-quality sequencing reads from 20 samples and have identified 757 amplicon sequence variants (ASVs) from these samples. For subsequent analysis the number of sequencing reads per sample was normalized to 34,000 per sample. Alpha and beta diversity were analyzed to assess changes of the overall gut microbiota structure. Alpha diversity describes the overall gut microbiota structure within a single sample.
Microbiome Analysis: Beta Diversity	0.76 Bray-Curtis distance Interval 0.65 to 0.81

PRIMARY outcome

Timeframe: Week 4

Population: For beta diversity, Bray-Curtis dissimilarity index was computed for each sample.

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

Outcome measures

Outcome measures
Measure	Microbiome Structure n=10 Participants In this pilot study, we collected 20 fecal samples from 10 subjects before and after the dietary intervention. We extracted the metagenomic DNA from the fecal samples and applied 16S rRNA gene amplicon sequencing to understand the impact of NBT-NM108 on the gut microbiome. We obtained \~980,000 high-quality sequencing reads from 20 samples and have identified 757 amplicon sequence variants (ASVs) from these samples. For subsequent analysis the number of sequencing reads per sample was normalized to 34,000 per sample. Alpha and beta diversity were analyzed to assess changes of the overall gut microbiota structure. Alpha diversity describes the overall gut microbiota structure within a single sample.
Microbiome Analysis: Beta Diversity	0.73 Bray-Curtis distance Interval 0.64 to 0.79

SECONDARY outcome

Timeframe: Week 4

Weight in kg

Outcome measures

Outcome measures
Measure	Microbiome Structure n=10 Participants In this pilot study, we collected 20 fecal samples from 10 subjects before and after the dietary intervention. We extracted the metagenomic DNA from the fecal samples and applied 16S rRNA gene amplicon sequencing to understand the impact of NBT-NM108 on the gut microbiome. We obtained \~980,000 high-quality sequencing reads from 20 samples and have identified 757 amplicon sequence variants (ASVs) from these samples. For subsequent analysis the number of sequencing reads per sample was normalized to 34,000 per sample. Alpha and beta diversity were analyzed to assess changes of the overall gut microbiota structure. Alpha diversity describes the overall gut microbiota structure within a single sample.
Weight	107 Kilogram Standard Deviation 22

SECONDARY outcome

Timeframe: Week 0

Population: Looking at iAUC for early and late response phases after meal.

Early response to meal post-intervention is 0-30min. Late response phase to meal post-intervention is 60-180min.

Outcome measures

Outcome measures
Measure	Microbiome Structure n=10 Participants In this pilot study, we collected 20 fecal samples from 10 subjects before and after the dietary intervention. We extracted the metagenomic DNA from the fecal samples and applied 16S rRNA gene amplicon sequencing to understand the impact of NBT-NM108 on the gut microbiome. We obtained \~980,000 high-quality sequencing reads from 20 samples and have identified 757 amplicon sequence variants (ASVs) from these samples. For subsequent analysis the number of sequencing reads per sample was normalized to 34,000 per sample. Alpha and beta diversity were analyzed to assess changes of the overall gut microbiota structure. Alpha diversity describes the overall gut microbiota structure within a single sample.
Acyl-Ghrelin Level Early Response	13.47 pg*min/mL Standard Deviation 22.54
Acyl-Ghrelin Level Late Response	187 pg*min/mL Standard Deviation 191

SECONDARY outcome

Timeframe: Week 4

Population: Looking at iAUC for early and late response phases after meal.

Early response to meal post-intervention is 0-30min. Late response phase to meal post-intervention is 60-180min.

Outcome measures

Outcome measures
Measure	Microbiome Structure n=10 Participants In this pilot study, we collected 20 fecal samples from 10 subjects before and after the dietary intervention. We extracted the metagenomic DNA from the fecal samples and applied 16S rRNA gene amplicon sequencing to understand the impact of NBT-NM108 on the gut microbiome. We obtained \~980,000 high-quality sequencing reads from 20 samples and have identified 757 amplicon sequence variants (ASVs) from these samples. For subsequent analysis the number of sequencing reads per sample was normalized to 34,000 per sample. Alpha and beta diversity were analyzed to assess changes of the overall gut microbiota structure. Alpha diversity describes the overall gut microbiota structure within a single sample.
Acyl-Ghrelin Level Early Response	12.5 pg*min/mL Standard Deviation 17.6
Acyl-Ghrelin Level Late Response	278 pg*min/mL Standard Deviation 605

SECONDARY outcome

Timeframe: Week 0

Population: Looking at iAUC for early and late response phases after meal.

Early response to meal post-intervention is 0-30min. Late response phase to meal post-intervention is 60-180min.