None listed
Conditions
Brief summary
Hypothesis: Gut microbiome transfer will lead to weight reduction and improvement in metabolism in obese adolescents. Aims: To determine whether gut microbiome transfer in severely obese adolescents will: (i) reduce body mass index (BMI) adjusted for age and sex (ii) improve body composition (iii) improve insulin sensitivity Background Gut microbiome transfer (GMT) in mice demonstrates the critical role of gut bacteria (i.e. the gut microbiome) in weight regulation at many levels: increased calorie absorption from non-digestible carbohydrates; impairment of the gut mucosal barrier; and production of bacterial products that pass into the host circulation (which are pro-inflammatory, promote adipogenesis, and have an effect on appetite). In humans, an association has been found between obesity and gut microbiome dysbiosis, with reduced bacterial diversity and over-abundance of obesogenic bacteria from the Firmicutes phylum. GMT is the first-line treatment for recurrent chronic Clostridium difficile colitis, curing ~90% of cases with remarkably few adverse events. In addition, a small pilot study showed that GMT improved insulin action in adults with type 2 diabetes. GMT has not been evaluated for the treatment of human obesity. We propose to perform a novel gold-standard clinical trial using encapsulated material to demonstrate the effectiveness of GMT for the treatment of severe obesity in adolescents. Subjects We will recruit 4 male and 4 female gut microbiome donors who are fit lean adults aged 18-28 years. These donors will provide fresh stools throughout the trial to be encapsuled for treatment. We will recruit 80 obese (BMI more or equal 30 kg/m2) adolescents (14-18 years), who will be randomly allocated into two groups: 40 control (placebo – capsules containing saline solution) or 40 treatment (capsules containing GMT). Recipients will undergo bowel cleansing with Glycoprep-C the evening before the GMT to optimise donor bacterial colonisation. Subsequently, recipients will receive 28 capsules of placebo or treatment over two consecutive mornings (16 on first day and 12 on second day). Clinical assessments will be performed at baseline, 6, 12, and 26 weeks.
Interventions
We will recruit 8 donors (4 males and 4 females), as recipients will only receive gut microbiome from donors of the same sex. Donors will be selected based on a strict inclusion criteria. Each donor is expected to produce a wet stool sample weighing 100-150 g. Stool samples will be collected and immediately processed for encapsulation. Capsules from each sample will be individually coded, so that each recipient will receive an equal number of capsules (n=7) from each of the 4 same sex donors.
We will recruit 8 donors (4 males and 4 females), as recipients will only receive gut microbiome from donors of the same sex. Donors will be selected based on a strict inclusion criteria. Each donor is expected to produce a wet stool sample weighing 100-150 g. Stool samples will be collected and immediately processed for encapsulation. Capsules from each sample will be individually coded, so that each recipient will receive an equal number of capsules (n=7) from each of the 4 same sex donors. Immediately after donation, stools are placed in normal saline, blended, and sieved to remove particulate matter. Samples are then differentially centrifuged to isolate a bacterial pellet. The bacterial pellet is suspended in normal saline (containing 15% glycerol – a cryoprotectant) at 0.5 g wet weight/ml before being dispensed into size 0 DRcapsTM capsules (Capsugel Inc, Sydney, Australia). The size 0 capsules are closed and secondarily sealed in size 00 DRcapsTM capsules. These capsules mask taste, odour, and visual appearance, and are designed to remain intact during passage through the stomach, delivering their contents to the intestine. Capsules are stored frozen at -80°C. We will recruit 80 obese adolescents aged 14-18 with BMI more or equal 30 kg/m2 randomised into two groups: control (placebo – saline) or treatment (gut microbiome transfer). Participants (recipients) will undergo bowel cleansing with Glycoprep-C® the evening before treatment initiation. The next morning, at the clinical research unit, each recipient in the placebo group will receive saline capsules, while those in the treatment group will receive gut microbiome capsules. Each recipient will receive a total of 28 capsules administered over two consecutive mornings under direct supervision from research staff, specifically 16 capsules on the first morning and 12 capsules on the second morning. Recipients will be fasting overnight for at least 8 hours prior to taking each set of capsules at the clinical research unit. After treatment, all recipients will remain fasting for another 2 hours. Recipients will be advised not to change their diet and physical activity and behaviour during the trial.
Sponsors
University of Auckland
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
14 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
Recipient subjects (40 males and 40 females): • Age 14-18 years • Obese (BMI: greater or equal than 30 kg/m2) • Post-pubertal (Tanner stage 5) Gut microbiome donors: • Age 18-28 years • BMI greater than 18.5 kg/m2 and less than 30.0 kg/m2 • Total body fat percentage: less than or equal to 29% for females; less than or equal to 19% for males • Regular exercise (moderate to vigorous physical activity for at least 3.5 hours/week) • Regular Bowel Habit (at least 1 every 2 days) • Intake greater than or equal to 4 portions of fruit and/or vegetables per day
Exclusion criteria
Donors: • Any transmissible viral or bacterial pathogens, or intestinal parasites • Multidrug-resistant organisms (e.g. vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Enterobacteriaceae, and carbapenem-resistant Enterobacteriaceae) • Gastrointestinal disease (including symptoms of irritable bowel syndrome, inflammatory bowel disease, or coeliac disease) • Atopic diseases requiring regular prophylaxis or treatment • Current or past history of malignancy • Impaired fasting glucose or impaired glucose tolerance • Type 1 diabetes, type 2 diabetes, or monogenic diabetes • Known dyslipidaemia, hypertension, or metabolic syndrome • Regular use of medications known to influence metabolism or the gut microbiome • Use of oral antibiotics in the past three months • Regular 'binge drinking', i.e. consumption of 5 or more standard drinks of alcohol per session, at least once a week • Any use of recreational drugs or tobacco • Current or past pregnancy • Overseas travel in previous 6 months, except for visits to Australia, UK, USA, Canada, Northern Europe, France, and Germany. • UK residence in 1980–1996 (due to risk of variant Creutzfeldt-Jakob disease) Recipients: •Gastrointestinal disease (including inflammatory bowel disease or coeliac disease) •Use of regular medications that may influence weight, metabolism, or the gut microbiome (including oral oestrogen-containing contraceptives, antidepressants, glucose-lowering drugs, diet drugs, as well as inhaled, topical, or oral steroids) •Consumption of probiotics •Type 1 diabetes, type 2 diabetes, or monogenic diabetes •Chronic diseases that could affect the primary outcome (other than obesity-related conditions) •Food allergies •Allergy to macrogol (active ingredient in the bowel preparation product) •Allergy to any over-the-counter medication •No antibiotic usage for three months prior to trial treatment
Outcome results
None listed