Obesity, Prader-Willi Syndrome
Conditions
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.
Interventions
DRUGNBT-NM108
All patients will consume NBT-NM108 in the form of 2 muffins daily.
Sponsors
Rutgers, The State University of New Jersey
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Microbiome Analysis: Alpha Diversity | Weeks 0 | 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. |
| Microbiome Analysis: Beta Diversity | Week 0 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peptide YY (PYY) | Week 0 | Early response to meal post-intervention is 0-30min. Late response phase to meal post-intervention is 60-180min. |
| Glucagon Like Peptide 1 (GLP1) | Week 0 | GLP1 levels were measured in patients before fiber intervention. Early response to meal post-intervention is 0-30min. Late response phase to meal post-intervention is 60-180min. |
| Insulin Level | Week 0 | Insulin levels were measured in patients before fiber intervention. Early response to meal post-intervention is 0-30min. Late response phase to meal post-intervention is 60-180min. |
| Weight | Week 4 | Weight in kg |
| Calorie Count | Week 0 | 24 hour dietary recall recorded in MyFitnessPal application measured in kcal. |
| Hyperphagia Questionnaire | Week 0 | Appetite behavior measured by questionnaire measured by likert scale. The scores should improve from week 0 to week 4. Higher scores indicate worse hyperphagia. |
| Glucose Level | Week 0 | Glucose levels were measured in patients before fiber intervention. Early phase (0-30min) and late phase response (60-180min) to a mixed meal tolerance test was collected. |
| Acyl-Ghrelin Level | Week 0 | Early response to meal post-intervention is 0-30min. Late response phase to meal post-intervention is 60-180min. |
Countries
United States
Participant flow
Recruitment details
Recruitment time period was from 11/1/2022 to 3/1/2023. Recruitment occurred from Robert Wood Johnson medical clinics.
Pre-assignment details
No patients were excluded from the study before assignment to arms or groups.
Participants by arm
| Arm | Count |
|---|---|
| Fiber Intervention All patients were given 48 grams of NBT-NM108 dietary fiber in the form of 2 muffins per day | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Fiber Intervention | — |
|---|---|---|
| Age, Continuous | 28 Years STANDARD_DEVIATION 9 | — |
| BMI | 38.58 kg/m^2 STANDARD_DEVIATION 7.82 | — |
| Diastolic Blood Pressure | 88.91 mmHg STANDARD_DEVIATION 9.63 | — |
| Heart Rate | 81.55 Beats per minute STANDARD_DEVIATION 15.92 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 12 Participants | — |
| Sex: Female, Male Female | 9 Participants | — |
| Sex: Female, Male Male | 3 Participants | — |
| Systolic Blood Pressure | 135 mmHg STANDARD_DEVIATION 13.64 | — |
| Weight | 107.01 kilogram STANDARD_DEVIATION 21.33 | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
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.
Time frame: Week 4
Population: For alpha diversity, Shannon index was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Microbiome Structure | Microbiome Analysis: Alpha Diversity | 4.73 Shannon index | Standard Deviation 0.41 |
Primary
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Microbiome Structure | Microbiome Analysis: Alpha Diversity | 4.89 Shannon index | Standard Deviation 0.46 |
Primary
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
Time frame: Week 4
Population: For beta diversity, Bray-Curtis dissimilarity index was computed for each sample.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Microbiome Structure | Microbiome Analysis: Beta Diversity | 0.73 Bray-Curtis distance |
Primary
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
Time frame: 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).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Microbiome Structure | Microbiome Analysis: Beta Diversity | 0.76 Bray-Curtis distance |
Secondary
Acyl-Ghrelin Level
Early response to meal post-intervention is 0-30min. Late response phase to meal post-intervention is 60-180min.
Time frame: Week 0
Population: Looking at iAUC for early and late response phases after meal.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Microbiome Structure | Acyl-Ghrelin Level | Early Response | 13.47 pg*min/mL | Standard Deviation 22.54 |
| Microbiome Structure | Acyl-Ghrelin Level | Late Response | 187 pg*min/mL | Standard Deviation 191 |
Secondary
Acyl-Ghrelin Level
Early response to meal post-intervention is 0-30min. Late response phase to meal post-intervention is 60-180min.
Time frame: Week 4
Population: Looking at iAUC for early and late response phases after meal.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Microbiome Structure | Acyl-Ghrelin Level | Early Response | 12.5 pg*min/mL | Standard Deviation 17.6 |
| Microbiome Structure | Acyl-Ghrelin Level | Late Response | 278 pg*min/mL | Standard Deviation 605 |
Secondary
Calorie Count
24 hour dietary recall recorded in MyFitnessPal application measured in kcal.
Time frame: Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Microbiome Structure | Calorie Count | 1840 Kcal | Standard Deviation 564 |
Secondary
Calorie Count
24 hour dietary recall recorded in MyFitnessPal application measured in kcal.
Time frame: Week 0
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Microbiome Structure | Calorie Count | 1638 Kcal | Standard Deviation 493 |
Secondary
Glucagon Like Peptide 1 (GLP1)
GLP1 levels were measured in patients after fiber intervention. Early response to meal post-intervention is 0-30min. Late response phase to meal post-intervention is 60-180min.
Time frame: Week 4
Population: Looking at iAUC for early and late response phase after meal.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Microbiome Structure | Glucagon Like Peptide 1 (GLP1) | early phase (0-30min) | 4.44 pg*min/ml | Standard Deviation 6.85 |
| Microbiome Structure | Glucagon Like Peptide 1 (GLP1) | late phase response (60-180min) | 79.6 pg*min/ml | Standard Deviation 55.7 |
Secondary
Glucagon Like Peptide 1 (GLP1)
GLP1 levels were measured in patients before fiber intervention. Early response to meal post-intervention is 0-30min. Late response phase to meal post-intervention is 60-180min.
Time frame: Week 0
Population: Looking at iAUC for early and late response phase after meal.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Microbiome Structure | Glucagon Like Peptide 1 (GLP1) | early phase (0-30min) | 10.6 pg*min/ml | Standard Deviation 15.8 |
| Microbiome Structure | Glucagon Like Peptide 1 (GLP1) | late phase response (60-180min) | 115 pg*min/ml | Standard Deviation 184 |
Secondary
Glucose Level
Glucose levels were measured in patients before fiber intervention. Early phase (0-30min) and late phase response (60-180min) to a mixed meal tolerance test was collected.
Time frame: Week 0
Population: Looking at iAUC for early and late response phase after meal.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Microbiome Structure | Glucose Level | early phase (0-30min) | 264 mmol*min/mL | Standard Deviation 288 |
| Microbiome Structure | Glucose Level | late phase response (60-180min) | 301 mmol*min/mL | Standard Deviation 503 |
Secondary
Glucose Level
Glucose levels were measured in patients after fiber intervention. Early phase (0-30min) and late phase response (60-180min) to a mixed meal tolerance test was collected.
Time frame: Week 4
Population: Glucose levels were measured in patients after fiber intervention. Early phase (0-30min) and late phase response (60-180min) to a mixed meal tolerance test was collected.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Microbiome Structure | Glucose Level | early phase (0-30min) | 182 mmol/L | Standard Deviation 222 |
| Microbiome Structure | Glucose Level | late phase response (60-180min) | 375 mmol/L | Standard Deviation 552 |
Secondary
Hyperphagia Questionnaire
Appetite behavior measured by questionnaire measured by likert scale. The scores should improve from week 0 to week 4. Higher scores indicate worse hyperphagia.
Time frame: Week 0
Population: The questionnaire includes 11 questions measured on a 5-point Likert scale, which are summarized in a total hyperphagia score (range: 11-55). Three subscores were summed: hyperphagic behavior (range: 5-25), hyperphagic drive (range: 4-20) and hyperphagic severity (range: 2-10). The scores should improve from week 0 to week 4 with intervention. Higher scores indicate worse hyperphagia. Our scores reported below are mean +/- standard deviation and not ranges.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Microbiome Structure | Hyperphagia Questionnaire | Hyperphagia behavior | 6.18 scores on a scale | Standard Deviation 1.83 |
| Microbiome Structure | Hyperphagia Questionnaire | Hyperphagia drive | 6.54 scores on a scale | Standard Deviation 2.2 |
| Microbiome Structure | Hyperphagia Questionnaire | Hyperphagia severity | 3.63 scores on a scale | Standard Deviation 1.69 |
Secondary
Hyperphagia Questionnaire
Appetite behavior measured by questionnaire measured by likert scale. The scores should improve from week 0 to week 4. Higher scores indicate worse hyperphagia. The questionnaire includes 11 questions measured on a 5-point Likert scale, which are summarized in a total hyperphagia score (range: 11-55). Three subscores were summed: hyperphagic behavior (range: 5-25), hyperphagic drive (range: 4-20) and hyperphagic severity (range: 2-10). The scores should improve from week 0 to week 4 with intervention. Higher scores indicate worse hyperphagia.
Time frame: Week 4
Population: The questionnaire includes 11 questions measured on a 5-point Likert scale, which are summarized in a total hyperphagia score (range: 11-55). Three subscores were summed: hyperphagic behavior (range: 5-25), hyperphagic drive (range: 4-20) and hyperphagic severity (range: 2-10). The scores should improve from week 0 to week 4 with intervention. Higher scores indicate worse hyperphagia. Our scores reported below are mean +/- standard deviation and not ranges.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Microbiome Structure | Hyperphagia Questionnaire | Hyperphagia severity | 3.1 scores on a scale | Standard Deviation 1.4 |
| Microbiome Structure | Hyperphagia Questionnaire | Hyperphagia behavior | 5.3 scores on a scale | Standard Deviation 1.7 |
| Microbiome Structure | Hyperphagia Questionnaire | Hyperphagia drive | 5.7 scores on a scale | Standard Deviation 1.7 |
Secondary
Insulin Level
Insulin levels were measured in patients after fiber intervention. Early response to meal post-intervention is 0-30min. Late response phase to meal post-intervention is 60-180min.
Time frame: Week 4
Population: Looking at iAUC for early and late response phase after meal.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Microbiome Structure | Insulin Level | late phase response (60-180min) | 7427 µIU*min/ml | Standard Deviation 3644 |
| Microbiome Structure | Insulin Level | early phase (0-30min) | 1607 µIU*min/ml | Standard Deviation 783 |
Secondary
Insulin Level
Insulin levels were measured in patients before fiber intervention. Early response to meal post-intervention is 0-30min. Late response phase to meal post-intervention is 60-180min.
Time frame: Week 0
Population: Looking at iAUC for early and late response phase after meal.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Microbiome Structure | Insulin Level | early phase (0-30min) | 1660 µIU*min/ml | Standard Deviation 716 |
| Microbiome Structure | Insulin Level | late phase response (60-180min) | 6361 µIU*min/ml | Standard Deviation 3978 |
Secondary
Peptide YY (PYY)
Early response to meal post-intervention is 0-30min. Late response phase to meal post-intervention is 60-180min.
Time frame: Week 4
Population: Looking at iAUC for early and late response phase after meal.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Microbiome Structure | Peptide YY (PYY) | early phase (0-30min) | 0.614 pg*min/mL | Standard Deviation 1.43 |
| Microbiome Structure | Peptide YY (PYY) | late phase response (60-180min) | 11.1 pg*min/mL | Standard Deviation 14.1 |
Secondary
Peptide YY (PYY)
Early response to meal post-intervention is 0-30min. Late response phase to meal post-intervention is 60-180min.
Time frame: Week 0
Population: Looking at iAUC for early and late response phases after meal.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Microbiome Structure | Peptide YY (PYY) | early phase (0-30min) | 0.23 pg*min/mL | Standard Deviation 0.37 |
| Microbiome Structure | Peptide YY (PYY) | late phase response (60-180min) | 4.01 pg*min/mL | Standard Deviation 4.22 |
Secondary
Weight
Weight in kg
Time frame: Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Microbiome Structure | Weight | 107 Kilogram | Standard Deviation 22 |