insulin resistance metabolic syndrome
Conditions
Interventions
Twelve MetSyn subjects will receive PBS (placebo) whereas another group of
twelve MetSyn subjects will receive a fecal filtrate transplant (FFT), which
lacks bacteria and mainly consists of phages.
Sponsors
Academisch Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Participants: • Caucasian male/female • Age: >=18 years old • BMI: >=25 kg/m2 • At least 3 of the following criteria: o Fasting plasma glucose >=5.6 mmol/L OR HOMA-IR index >=2.5 o Waist-circumference >=102 cm o HDL cholesterol =130/85 mmHg o Triglycerides >=1.7 mmol/L • Subjects should be able to give informed consent Donors: • Caucasian male/female • Age: >18 years old • BMI: 18-25 kg/m2 • Subjects should be able to give informed consent
Exclusion criteria
Exclusion criteria: Participants: • A history of cardiovascular event (cerebrovascular accident (CVA), myocardial infarction (MI)) or pacemaker implantation • Use of any medication including proton pump inhibitors, antibiotics and pro-/prebiotics in the past three months or during the study period • (Expected) prolonged compromised immunity (due to recent cytotoxic chemotherapy or human immunodeficiency viruses (HIV) infection with a CD4 count =3 stools/day for >4 weeks), chronic obstipation (3 months), Irritable Bowel Syndrome (IBS) (according to Rome IV criteria) or Inflammatory Bowel Disease (IBD). • Smoking or illicit drug use (MDMA/amphetamine/cocaine/heroin/GHB) in the past three months or use during the study period • Use of >5 units of alcohol daily on average in the past three months or use of >2 units of alcohol during the study period • History of cholecystectomy Donors: • Use of any medication including proton pump inhibitors, antibiotics and pro-/prebiotics in the past three months or during the study period • History of, or known exposure to HIV, hepatitis B (HBV) or C virus (HCV), syphilis, human T-lymphotropic virus (HTLV) I and II, malaria, trypanosomiasis, tuberculosis • Known systemic infection not controlled at the time of donation • Smoking or illicit drug use (MDMA/amphetamine/cocaine/heroin/GHB) in the past three months or use during the study period • Use of >5 units of alcohol daily on average in the past three months or use of >2 units of alcohol during the study period • Risky sexual behaviour (anonymous sexual contacts; sexual contacts with prostitutes, drug addicts, individuals with HIV, viral hepatitis, syphilis; work as prostitute; history of sexually transmittable disease) • Previous reception of tissue/organ transplant • Previous (=3 stools/day), hematochezia • History of neurological/neurodegenerative disorders • History of psychiatric conditions • Presence of chronic low grade inflammation or metabolic syndrome (NCEP criteria) • Presence of T1DM, T2DM or hypertension • History of cholecystectomy • P
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess and compare the effect of lean-donor phage transplantation with placebo on glucose tolerance in obese, insulin resistant subjects at risk to develop diabetes. HbA1c, fasted glucose and insulin levels will be determined at baseline and 28days after the intervention (prior to the OGTTs). Area under the curve for glucose excursion during OGTTs will be the primary determinant of changes in glucose metabolism following the transplantations. Furthermore, insulin sensitivity will be estimated from the OGTT by oral glucose insulin sensitivity (OGIS) methodology. In addition, HOMA-IR and Matsuda index will be calculated as secondary readouts for insulin sensitivity. | — |
Secondary
| Measure | Time frame |
|---|---|
| To assess and compare changes in gut microbiota and phage composition following phage transplantation and placebo. In addition, microbiota and virome composition at baseline will be determined and compared between lean donors and obese recipients. Bacterial and phage composition will be assessed by 16S rRNA analysis and NanoPore technology, resp., in fecal samples of donors and recipients. | — |
Countries
Netherlands
Outcome results
None listed