Metabolic SyndromePhase 1/2BROMONCT05971524
Effect of Oral 6-bromotryptophan on Safety, Pharmacokinetics and Efficacy in Metabolic Syndrome Individuals
A Phase 1/2 study testing 6-BT in people with Metabolic Syndrome and Diabetes Mellitus, run by Nordin Hanssen at 1 site in Netherlands.
Trial summary
Safety, pharmacokinetics and efficacy of a novel endogenous plasma metabolite, 6-bromotryptophan, will be established in metabolic syndrome/ insulin resistant participants. Read more about this study
- Who is it for?
- Ages 35 to 70 years, men only
- Conditions the study is for
- Metabolic Syndrome, Diabetes Mellitus
- What is being tested?
- 6-BT
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteNetherlands
- Study dates
- 4 May 2023to 1 Feb 2025
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 70 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Metabolic syndrome, defined as:
- ≥3 criteria out of the 5 following criteria:
- fasting plasma glucose ≥5.6 mmol/L
- triglycerides ≥1.7 mmol/L
- waist circumference ≥102 cm
- high-density lipoprotein cholesterol ≤1.04 mmol/
Show all 11Show fewer
- blood pressure ≥130/85 mm Hg.
- AND/ OR Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (>2.5)
- Male
- Caucasian
- 35-70 years old
Who cannot join
- 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
- Exclusion criterion for MRI liver (see E4_BROMO_vragenlijst MRI)
- Alcohol abuse
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Amsterdam UMC
Amsterdam, North Holland, 1105AZ
N Hanssen, dr, 020-5669111, n.m.j.hanssen@amsterdamumc.nl
About this study
Official title: Effect of 4 Weeks of Oral 6-bromotryptophan on Safety, Pharmacokinetics and Efficacy in Metabolic Syndrome Individuals (2022)
Safety, pharmacokinetics and efficacy of a novel endogenous plasma metabolite, 6-bromotryptophan, will be established in metabolic syndrome/ insulin resistant participants.
Read the detailed description
Rationale:
A newly identified endogenous plasma microbiome-derived tryptophan metabolite, 6-bromotryptophan (6-BT), 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 the investigators progress to an efficacy study in T1D, the investigators 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.
Objective: To assess safety, pharmacokinetics and efficacy of oral dosage of 6-BT in individuals with metabolic syndrome Study design: A phase I/II, dose finding, placebo controlled, double blinded trial.
Study population: Metabolic syndrome individuals or participants with insulin resistance, age 35-70 years, without use of medication.
Intervention (if applicable): 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).
Main study parameters/endpoints:
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 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 ribosomal ribonucleic acid (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, the investigators will also study its pharmacokinetics by measuring serum 6-BT concentrations in serum and urine at different time-points after oral intake.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
6-BT is an 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. Hence, the investigators do not foresee major adverse reactions. As there is an urgent need for halting diabetes progression, patients would benefit from the development of new endogenously occurring therapeutic agents.
- Conditions
- Metabolic Syndrome, Diabetes Mellitus
- Being tested
- 6-BT, Placebo
- Medical subject headings
- Metabolic Syndrome, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
6-BTDietary supplement
2,4 or 8mg of 6-BT once daily for 4 weeks
PlaceboDietary supplement
A placebo capsule once daily for 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | An oral placebo capsule once daily for 4 weeks Receives: Dietary Supplement: Placebo |
| 2mg 6-BT | Experimental | 2 mg of 6-BT as an oral capsule once daily for 4 weeks Receives: Dietary Supplement: 6-BT |
| 4mg 6-BT | Experimental | 4 mg of 6-BT as an oral capsule once daily for 4 weeks Receives: Dietary Supplement: 6-BT |
| 8mg 6-BT | Experimental | 8 mg of 6-BT as an oral capsule once daily for 4 weeks Receives: Dietary Supplement: 6-BT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events
Number of adverse events
Measured: 4 weeks
renal function
Number of participants with a decreased kidney function, defined as a rise in serum creatinine of >26,5 micromol/L in 48 h
Measured: 4 weeks
Questionnaires
Changes in Gastro-intestinal Quality of Life Index (GIQLI score) (points). The minimum and maximum score are 31 and 155 points respectively, and a higher score reflects a better outcome.
Measured: 4 weeks
Occurence of anemia
Number of patients with Hb < 8,5 mmol/L
Measured: 4 weeks
Changes in leucocytes
Number of patients with leucocytes <4,0 or >10,5 x10E9 cells/L
Measured: 4 weeks
Changes in trombocytes
Number of patients with trombocytes <150 x 10E9 cells/L
Measured: 4 weeks
Changes in aspartate aminotransferase (AST)
Number of patients with AST > 43 IU/L
Measured: 4 weeks
Changes in alanine aminotransferas (ALT)
Number of patients with ALT > 45 IU/L
Measured: 4 weeks
Changes in alkaline phosphatase (ALP)
Number of patients with ALP > 126 IU/L
Measured: 4 weeks
Changes in Gamma-glutamyltransferase (GGT)
Number of patients with GGT > 117 IU/L
Measured: 4 weeks
Changes in total bilirubin
Number of patients with total bilirubin > 24 micromol/L
Measured: 4 weeks
Mixed meal test
Changes in area under the curve (AUC) of glucose after mixed-meal test
Measured: 4 weeks
Mixed meal test
Changes in area under the curve (AUC) of insulin after mixed-meal test
Measured: 4 weeks
Time-in-range
Increase in Time-in-range (TIR,%), a parameter of continuous glucose monitoring devices, where TIR can be between 0 and 100%. A higher TIR reflects a better outcome.
Measured: 4 weeks
Continuous glucose monitoring
Decrease in glucose variability (GV, %), a parameter of continuous glucose monitoring devices, where GV can be between 0 and 100%. A lower GV reflects a better outcome.
Measured: 4 weeks
Glycemic control
Changes in fasting glucose (mmol/L)
Measured: 4 weeks
Secondary outcomes (9)
Intestinal microbiota composition
Changes from baseline of relative abundance (%) of bacterial phyla, genera and species between groups and within participants.
Measured: 4 weeks
Immunologic profile
Absolute counts of different immunologic cell types using Cytometry by time of flight (CyTOF) mass cytometry at baseline, 4 weeks and 6 weeks.
Measured: 6 weeks
6-BT pharmacokinetics
Quantitatively measuring plasma concentrations of 6-BT at -15, 30, 60, 90, 120, 240 and 300 minutes following 6-BT capsule ingestion
Measured: 6-BT pharmacokinetics as described above will be performed at baseline and after 4 weeks.
Hepatic stiffness
Hepatic stiffness will be determined non-invasively by MRI using a special hepatic scanning protocol of 30 minutes
Measured: 0 and 4 weeks
Hepatic fat content
Hepatic fat content will be determined non-invasively by MRI using a special hepatic scanning protocol of 30 minutes
Measured: 0 and 4 weeks
Dietary intake
Participants are asked to fill out an online dietary questionnaire for the 3 days prior to study visit 2,3,4,5 and 7
Measured: 4 weeks
Low-density lipoprotein (LDL)
Changes in LDL (mmol/L)
Measured: 4 weeks
High-density lipoprotein (HDL)
Changes in HDL (mmol/L)
Measured: 4 weeks
Triglycerides
Changes in triglycerides (mmol/L)
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2023
- Study start4 May 2023
- Primary completion1 Feb 2025 (estimated)
- Study completion1 Feb 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metabolic SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A phase I/II, dose finding, placebo controlled, double blinded trial
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nordin Hanssen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Nordin Hanssen, Amsterdam University Medical Centers (UMC), Location Academic Medical Center (AMC)
- Investigators
- Nordin MJ Hanssen, dr., Principal investigator, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05971524
- Sponsor's protocol ID
- NL83061.018.22
- Acronym
- BROMO
- Status last verified
- Aug 2023
- First submitted
- 20 Apr 2023
- Last updated
- 22 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of 4 Weeks of Oral 6-bromotryptophan on Safety, Pharmacokinetics and Efficacy in Metabolic Syndrome Individuals (2022)
- ClinicalTrials.gov ID
- NCT05971524
- Acronym / sponsor ID
- BROMO / NL83061.018.22
- Conditions
- Metabolic Syndrome, Diabetes Mellitus
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Nordin HanssenUniversity, hospital or other
- Study start
- 4 May 2023 (actual)
- Primary completion
- 1 Feb 2025 (estimated)
- Study completion
- 1 Feb 2025 (estimated)
- First posted
- 2 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Safety, pharmacokinetics and efficacy of a novel endogenous plasma metabolite, 6-bromotryptophan, will be established in metabolic syndrome/ insulin resistant participants.
Detailed description
Rationale:
A newly identified endogenous plasma microbiome-derived tryptophan metabolite, 6-bromotryptophan (6-BT), 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 the investigators progress to an efficacy study in T1D, the investigators 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.
Objective: To assess safety, pharmacokinetics and efficacy of oral dosage of 6-BT in individuals with metabolic syndrome Study design: A phase I/II, dose finding, placebo controlled, double blinded trial.
Study population: Metabolic syndrome individuals or participants with insulin resistance, age 35-70 years, without use of medication.
Intervention (if applicable): 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).
Main study parameters/endpoints:
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 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 ribosomal ribonucleic acid (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, the investigators will also study its pharmacokinetics by measuring serum 6-BT concentrations in serum and urine at different time-points after oral intake.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
6-BT is an 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. Hence, the investigators do not foresee major adverse reactions. As there is an urgent need for halting diabetes progression, patients would benefit from the development of new endogenously occurring therapeutic agents.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
- Model description
- A phase I/II, dose finding, placebo controlled, double blinded trial
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Dietary Supplement: PlaceboAn oral placebo capsule once daily for 4 weeks |
| 2mg 6-BT | Experimental | Dietary Supplement: 6-BT2 mg of 6-BT as an oral capsule once daily for 4 weeks |
| 4mg 6-BT | Experimental | Dietary Supplement: 6-BT4 mg of 6-BT as an oral capsule once daily for 4 weeks |
| 8mg 6-BT | Experimental | Dietary Supplement: 6-BT8 mg of 6-BT as an oral capsule once daily for 4 weeks |
Who may qualify
- Ages
- 35 to 70 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Metabolic syndrome, defined as:
- ≥3 criteria out of the 5 following criteria:
- fasting plasma glucose ≥5.6 mmol/L
- triglycerides ≥1.7 mmol/L
- waist circumference ≥102 cm
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 6-BT2,4 or 8mg of 6-BT once daily for 4 weeks | Dietary supplement | 2mg 6-BT, 4mg 6-BT, 8mg 6-BT |
| PlaceboA placebo capsule once daily for 4 weeks | Dietary supplement | Placebo |
Primary outcome
Adverse events
Time frame: 4 weeks
Number of adverse events
renal function
Time frame: 4 weeks
Number of participants with a decreased kidney function, defined as a rise in serum creatinine of >26,5 micromol/L in 48 h
Questionnaires
Time frame: 4 weeks
Changes in Gastro-intestinal Quality of Life Index (GIQLI score) (points). The minimum and maximum score are 31 and 155 points respectively, and a higher score reflects a better outcome.
Occurence of anemia
Time frame: 4 weeks
Number of patients with Hb < 8,5 mmol/L
Changes in leucocytes
Time frame: 4 weeks
Number of patients with leucocytes <4,0 or >10,5 x10E9 cells/L
Changes in trombocytes
Time frame: 4 weeks
Number of patients with trombocytes <150 x 10E9 cells/L
Changes in aspartate aminotransferase (AST)
Time frame: 4 weeks
Number of patients with AST > 43 IU/L
Changes in alanine aminotransferas (ALT)
Time frame: 4 weeks
Number of patients with ALT > 45 IU/L
Changes in alkaline phosphatase (ALP)
Time frame: 4 weeks
Number of patients with ALP > 126 IU/L
Changes in Gamma-glutamyltransferase (GGT)
Time frame: 4 weeks
Number of patients with GGT > 117 IU/L
Changes in total bilirubin
Time frame: 4 weeks
Number of patients with total bilirubin > 24 micromol/L
Mixed meal test
Time frame: 4 weeks
Changes in area under the curve (AUC) of glucose after mixed-meal test
Mixed meal test
Time frame: 4 weeks
Changes in area under the curve (AUC) of insulin after mixed-meal test
Time-in-range
Time frame: 4 weeks
Increase in Time-in-range (TIR,%), a parameter of continuous glucose monitoring devices, where TIR can be between 0 and 100%. A higher TIR reflects a better outcome.
Continuous glucose monitoring
Time frame: 4 weeks
Decrease in glucose variability (GV, %), a parameter of continuous glucose monitoring devices, where GV can be between 0 and 100%. A lower GV reflects a better outcome.
Glycemic control
Time frame: 4 weeks
Changes in fasting glucose (mmol/L)
9 secondary outcomes
Intestinal microbiota composition
Time frame: 4 weeks
Immunologic profile
Time frame: 6 weeks
6-BT pharmacokinetics
Time frame: 6-BT pharmacokinetics as described above will be performed at baseline and after 4 weeks.
Hepatic stiffness
Time frame: 0 and 4 weeks
Hepatic fat content
Time frame: 0 and 4 weeks
Dietary intake
Time frame: 4 weeks
Low-density lipoprotein (LDL)
Time frame: 4 weeks
High-density lipoprotein (HDL)
Time frame: 4 weeks
Triglycerides
Time frame: 4 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nordin MJ Hanssen, dr. principal investigator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing 6-BT in people with Metabolic Syndrome and Diabetes Mellitus, run by Nordin Hanssen at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Nordin MJ Hanssen, dr. (020-56691111, n.m.j.hanssen@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse events (time frame: 4 weeks). The study lists 16 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2023.