Back to resultsFiber and Metformin Combination Therapy in Adolescents With Severe Obesity and Insulin Resistance
Primary Purpose
Obesity, Childhood, Insulin Resistance
Status
Recruiting
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
Metformin 850 mg oral tablet bid
Supplemental fiber mixture (35 g total) composed of 6g of Oligofructose + 12g of resistant maltodextrin + 12g of acacia gum + 5g of PGX.
Sponsored by
About this trial
This is an interventional treatment trial for Obesity, Childhood focused on measuring Dietary fiber, Metformin
Eligibility Criteria
Inclusion Criteria:
- Age 12-18 years
- BMI percentile > 95% for age/sex;
- Total weight fluctuation over past 6 months < 10%;
- HOMA-IR > 3.16;
- FH of T2DM (first or second-degree relative).
Exclusion Criteria:
- Current use of insulin or diagnosis of T2DM;
- Systolic or diastolic blood pressure (BP) > 99th percentile for age and sex;
- Acute infectious or inflammatory condition over the preceding 1 month; hospitalization > 48 hrs;
- History of chronic disease such as inflammatory bowel disease, chronic severe liver or kidney disease or neurologic disorders;
- Active malignancy;
- Concomitant use of medication/investigational drug known to affect body weight in the past year;
- Antibiotic use in past 60 days; probiotic and/or prebiotic supplements use in the past 30 days; use of lipid-lowering and anti-inflammatory medication.
Sites / Locations
- University of AlbertaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Experimental
Arm Label
MET
FIBER
FIBER + MET
Arm Description
MET (850 mg po bid - standard of care) + Fiber placebo daily
Fiber supplementation [35g fiber daily] + MET placebo po bid
Fiber supplementation [35g fiber daily] + MET 850 mg po bid
Outcomes
Primary Outcome Measures
Changes in HOMA-IR
Change in HOMA-IR value
Secondary Outcome Measures
Changes in body weight
Body weight measured in kg
Changes in body mass index (BMI)
BMI percentile and z-score according to age and sex will be estimated
Changes in body composition
Body density using air-displacement plethysmography will be assessed to estimate fat mass and fat-free mass.
Changes in inflammation
Markers of inflammation that will be measured are: high-sensitivity C-reactive protein, interleukin, tumor necrosis factor-alpha)
Changes in metabolic function
The markers of metabolic function that will be measured are: fasting glucose, lipids (total, high and low density lipoprotein cholesterol; triglycerides), and oral glucose tolerance test.
Changes in satiety hormones
Markers of satiety that will be measured are: acylated ghrelin, peptide tyrosine tyrosine, GLP-1, leptin, and adiponectin.
Changes in quality of life
Quality of life will be measured by the a questionnaire
Changes in perceived hunger and satiety
Perceived hunger and satiety will be assessed by a questionnaire
Changes in gut microbiota composition
Fecal microbiota composition will be characterized by 16S rRNA gene amplicons sequencing using taxonomic and non-taxonomic based approaches.
Changes in gut microbiome functions
Fecal microbiome functions will be assessed through whole metagenomic sequencing, stool SCFAs and bile acids, and plasma metabolomics.
Changes in intestinal barrier integrity
Plasma lipopolysaccharide-binding protein and fecal calprotectin will be determined as measures of gut barrier integrity
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04578652
Brief Title
Fiber and Metformin Combination Therapy in Adolescents With Severe Obesity and Insulin Resistance
Official Title
Fiber Supplementation and Metformin Combination Therapy in Adolescents With Severe Obesity and Insulin Resistance: Interactions With the Gut Microbiome.
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 22, 2021 (Actual)
Primary Completion Date
September 2025 (Anticipated)
Study Completion Date
September 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Alberta
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a 12-month, single center, three-arm parallel design, double-blind, randomized clinical trial, to compare the effects of supplemental dietary fiber and metformin (MET) alone and in combination over 12 months on glucose metabolism (insulin resistance [IR]), inflammation and BMI in adolescents with obesity and IR, and to assess the relationship between therapeutic intervention(s) and changes in gut microbiome composition and function.
Since MET and FIBER have been shown to reduce weight and increase insulin sensitivity through distinct but overlapping mechanisms of action, our central hypothesis is that the combination of FIBER + MET will have a synergistic effect and be more effective than FIBER or MET alone in improving metabolic function (IR) and reducing BMI and inflammation in adolescents with obesity, IR and family history (FM) of T2DM.
.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity, Childhood, Insulin Resistance
Keywords
Dietary fiber, Metformin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Masking Description
Participants and research team will be blinded to the type of intervention allocated to each arm until the end of the study. Concealment will be protected by secure, password protected website. The group not on MET (fiber alone) will receive a placebo pill. The group not on fiber will also receive a placebo, composed of the same base solution without added fibers.
Allocation
Randomized
Enrollment
90 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
MET
Arm Type
Active Comparator
Arm Description
MET (850 mg po bid - standard of care) + Fiber placebo daily
Arm Title
FIBER
Arm Type
Active Comparator
Arm Description
Fiber supplementation [35g fiber daily] + MET placebo po bid
Arm Title
FIBER + MET
Arm Type
Experimental
Arm Description
Fiber supplementation [35g fiber daily] + MET 850 mg po bid
Intervention Type
Drug
Intervention Name(s)
Metformin 850 mg oral tablet bid
Intervention Description
MET dose: 500 mg daily, increasing to 500 bid if tolerated after 2 weeks, then increasing again 2 weeks later to 850 mg bid (1700 mg daily).
Intervention Type
Dietary Supplement
Intervention Name(s)
Supplemental fiber mixture (35 g total) composed of 6g of Oligofructose + 12g of resistant maltodextrin + 12g of acacia gum + 5g of PGX.
Intervention Description
The first week of treatment will use 1/3 the daily treatment dose; then 2/3 dose for the second and third weeks; then the full dose thereafter, to allow time for adaptation.
Primary Outcome Measure Information:
Title
Changes in HOMA-IR
Description
Change in HOMA-IR value
Time Frame
Baseline, 6, and 12 months
Secondary Outcome Measure Information:
Title
Changes in body weight
Description
Body weight measured in kg
Time Frame
Baseline, 6, and 12 months
Title
Changes in body mass index (BMI)
Description
BMI percentile and z-score according to age and sex will be estimated
Time Frame
Baseline, 6, and 12 months
Title
Changes in body composition
Description
Body density using air-displacement plethysmography will be assessed to estimate fat mass and fat-free mass.
Time Frame
Baseline, 6, and 12 months
Title
Changes in inflammation
Description
Markers of inflammation that will be measured are: high-sensitivity C-reactive protein, interleukin, tumor necrosis factor-alpha)
Time Frame
Baseline, 6, and 12 months
Title
Changes in metabolic function
Description
The markers of metabolic function that will be measured are: fasting glucose, lipids (total, high and low density lipoprotein cholesterol; triglycerides), and oral glucose tolerance test.
Time Frame
Baseline, 6, and 12 months
Title
Changes in satiety hormones
Description
Markers of satiety that will be measured are: acylated ghrelin, peptide tyrosine tyrosine, GLP-1, leptin, and adiponectin.
Time Frame
Baseline, 6, and 12 months
Title
Changes in quality of life
Description
Quality of life will be measured by the a questionnaire
Time Frame
Baseline, 6, and 12 months
Title
Changes in perceived hunger and satiety
Description
Perceived hunger and satiety will be assessed by a questionnaire
Time Frame
Baseline, 6, and 12 months
Title
Changes in gut microbiota composition
Description
Fecal microbiota composition will be characterized by 16S rRNA gene amplicons sequencing using taxonomic and non-taxonomic based approaches.
Time Frame
Baseline, 6, and 12 months
Title
Changes in gut microbiome functions
Description
Fecal microbiome functions will be assessed through whole metagenomic sequencing, stool SCFAs and bile acids, and plasma metabolomics.
Time Frame
Baseline, 6, and 12 months
Title
Changes in intestinal barrier integrity
Description
Plasma lipopolysaccharide-binding protein and fecal calprotectin will be determined as measures of gut barrier integrity
Time Frame
Baseline, 6, and 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 12-18 years
BMI percentile > 95% for age/sex;
Total weight fluctuation over past 6 months < 10%;
HOMA-IR > 3.16;
FH of T2DM (first or second-degree relative).
Exclusion Criteria:
Current use of insulin or diagnosis of T2DM;
Systolic or diastolic blood pressure (BP) > 99th percentile for age and sex;
Acute infectious or inflammatory condition over the preceding 1 month; hospitalization > 48 hrs;
History of chronic disease such as inflammatory bowel disease, chronic severe liver or kidney disease or neurologic disorders;
Active malignancy;
Concomitant use of medication/investigational drug known to affect body weight in the past year;
Antibiotic use in past 60 days; probiotic and/or prebiotic supplements use in the past 30 days; use of lipid-lowering and anti-inflammatory medication.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Andrea M Haqq, MD, MHS
Phone
780-492-0015
Email
haqq@ualberta.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrea M Haqq, MD, MHS
Organizational Affiliation
University of Alberta
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alberta
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2E1
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrea M Haqq, MD, MHS
Phone
780-492-0015
Email
haqq@ualberta.ca
First Name & Middle Initial & Last Name & Degree
Andrea M Haqq, MD, MHS
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
33596993
Citation
Deehan EC, Colin-Ramirez E, Triador L, Madsen KL, Prado CM, Field CJ, Ball GDC, Tan Q, Orsso C, Dinu I, Pakseresht M, Rubin D, Sharma AM, Tun H, Walter J, Newgard CB, Freemark M, Wine E, Haqq AM. Efficacy of metformin and fermentable fiber combination therapy in adolescents with severe obesity and insulin resistance: study protocol for a double-blind randomized controlled trial. Trials. 2021 Feb 17;22(1):148. doi: 10.1186/s13063-021-05060-8.
Results Reference
derived
Learn more about this trial
Fiber and Metformin Combination Therapy in Adolescents With Severe Obesity and Insulin Resistance
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