To assess safety, pharmacokinetics and efficacy of oral dosage of 6-BT in individuals with metabolic syndrome
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The principal outcome will be patient safety and tolerability (biochemical
parameters of kidney and liver function and complete blood count, adverse
events) in relation to improvements in glucose homeostasis (mixed-meal tests
and continuous glucose monitoring).
Secondary outcome
Secondary read-outs will include changes in: immunological profile (ex vivo
stimulation of monocytes, and immunophenotyping of peripheral blood mononuclear
cells (PBMC)) and gut microbiome composition (16s rRNA sequencing). Also, liver
fat content will be determined before and at end of the trial by MRI. As this
food derived metabolite is given to humans for the first time, we will also
study its pharmacokinetics by measuring serum 6-BT concentrations in serum and
urine at different time-points after oral intake.
Background summary
We identified a novel endogenous plasma microbiome-derived tryptophan
metabolite, 6-bromotryptophan (6-BT), which was associated with preserved
beta-cell function and diminished circulating T cell count in (T1D) type 1
diabetes patients. Anti-inflammatory and insulin-secratogogue effects were
established in in vitro- and murine studies in both the setting of type 1 and
type 2 diabetes. Also, 6-BT did not show any toxic effects in cells or in vivo
experiments. In order to obtain safety data before we progress to an efficacy
study in T1D, we aim to perform a phase I/II trial of 6-BT in metabolic
syndrome individuals. If safe, 6-BT may hold a promise as a food supplement in
type 1 and 2 diabetes.
Study objective
To assess safety, pharmacokinetics and efficacy of oral dosage of 6-BT in
individuals with metabolic syndrome
Study design
A double blinded, phase I/II, dose finding, placebo controlled trial.
Intervention
Participants will be given placebo, 2mg, 4mg or 8mg of 6-BT capsules once daily
for 4 weeks (n=9 per arm, total of 36 participants).
Study burden and risks
6-BT is a endogenous (food tryptophan derived) metabolite found in the human
circulation. Our previous trail has shown that fecal microbiota
transplantations (FMT) can modulate and increase plasma 6-BT levels with a
positive association with C-peptide (as marker of pancreatic beta cells
function). Additionally, recent investigations have linked higher plasma 6-BT
levels with lower risk of kidney disease progression, supporting the health
benefits of 6-BT beyond T1D.Also, previous human studies with bromo intake in
healthy subjects in much higher dosages was (see protocol chapter k 5.4) and
this 6BT food supplement was found to be safe and effective in mouse studies.
In tota l subjects will spend 19h on this study, and 403 ml blood will be
taken. Venapunction has a small risk of hematoma. MRI scan can be unpleasant
but has no health risk just like collecting 24-hours urine and feces.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
• Metabolic syndrome AND/OR insulin resistance, defined as:
* Metabolic syndrome: >=3 criteria out of the 5 following criteria:
o fasting plasma glucose >=5.6*mmol/L
o triglycerides >=1.7*mmol/L
o waist circumference >=102*cm
o high-density lipoprotein cholesterol <=1.04*mmol/
o blood pressure >=130/85*mm Hg.
* Insulin resistance: HOMA-IR (>2.5)
• Male
• Caucasian
• 35-70 years old
Exclusion criteria
- Use of systemic medication (except for paracetamol), including proton pump
inhibitors, antibiotics and pro-/prebiotics in the past three months or during
the study period.
- A history of a cardiovascular event
- A history of cholecystectomy
- Overt untreated gastrointestinal disease or abnormal bowel habits
- Liver enzymes>2.5*fold higher than the upper limit of normal range
- Smoking
- Alcohol abuse
- Exclusion criterion for MRI liver (metal in body, claustrophobic etc.)
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL83061.018.22 |