The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Effect of Oral 6-bromotryptophan on Safety, Pharmacokinetics and Efficacy in Metabolic Syndrome Individuals (BROMO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05971524
Recruitment Status : Recruiting
First Posted : August 2, 2023
Last Update Posted : August 22, 2023
Sponsor:
Information provided by (Responsible Party):
Nordin Hanssen, Amsterdam University Medical Centers (UMC), Location Academic Medical Center (AMC)

Brief Summary:
Safety, pharmacokinetics and efficacy of a novel endogenous plasma metabolite, 6-bromotryptophan, will be established in metabolic syndrome/ insulin resistant participants.

Condition or disease Intervention/treatment Phase
Metabolic Syndrome Diabetes Mellitus Dietary Supplement: 6-BT Dietary Supplement: Placebo Phase 1 Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: A phase I/II, dose finding, placebo controlled, double blinded trial
Masking: Double (Participant, Investigator)
Masking Description: To maintain the blinding of the subject and investigators, the identifying labels will be removed from the intervention product at the AMC pharmacy. The study product will be labelled with subject specific information prior to delivery to the study physician, who will hand over the intervention to the participant.
Primary Purpose: Treatment
Official Title: Effect of 4 Weeks of Oral 6-bromotryptophan on Safety, Pharmacokinetics and Efficacy in Metabolic Syndrome Individuals (2022)
Actual Study Start Date : May 4, 2023
Estimated Primary Completion Date : February 1, 2025
Estimated Study Completion Date : February 1, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo
An oral placebo capsule once daily for 4 weeks
Dietary Supplement: Placebo
A placebo capsule once daily for 4 weeks

Experimental: 2mg 6-BT
2 mg of 6-BT as an oral capsule once daily for 4 weeks
Dietary Supplement: 6-BT
2,4 or 8mg of 6-BT once daily for 4 weeks

Experimental: 4mg 6-BT
4 mg of 6-BT as an oral capsule once daily for 4 weeks
Dietary Supplement: 6-BT
2,4 or 8mg of 6-BT once daily for 4 weeks

Experimental: 8mg 6-BT
8 mg of 6-BT as an oral capsule once daily for 4 weeks
Dietary Supplement: 6-BT
2,4 or 8mg of 6-BT once daily for 4 weeks




Primary Outcome Measures :
  1. Adverse events [ Time Frame: 4 weeks ]
    Number of adverse events

  2. 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

  3. 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.

  4. Occurence of anemia [ Time Frame: 4 weeks ]
    Number of patients with Hb < 8,5 mmol/L

  5. Changes in leucocytes [ Time Frame: 4 weeks ]
    Number of patients with leucocytes <4,0 or >10,5 x10E9 cells/L

  6. Changes in trombocytes [ Time Frame: 4 weeks ]
    Number of patients with trombocytes <150 x 10E9 cells/L

  7. Changes in aspartate aminotransferase (AST) [ Time Frame: 4 weeks ]
    Number of patients with AST > 43 IU/L

  8. Changes in alanine aminotransferas (ALT) [ Time Frame: 4 weeks ]
    Number of patients with ALT > 45 IU/L

  9. Changes in alkaline phosphatase (ALP) [ Time Frame: 4 weeks ]
    Number of patients with ALP > 126 IU/L

  10. Changes in Gamma-glutamyltransferase (GGT) [ Time Frame: 4 weeks ]
    Number of patients with GGT > 117 IU/L

  11. Changes in total bilirubin [ Time Frame: 4 weeks ]
    Number of patients with total bilirubin > 24 micromol/L

  12. Mixed meal test [ Time Frame: 4 weeks ]
    Changes in area under the curve (AUC) of glucose after mixed-meal test

  13. Mixed meal test [ Time Frame: 4 weeks ]
    Changes in area under the curve (AUC) of insulin after mixed-meal test

  14. 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.

  15. 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.

  16. Glycemic control [ Time Frame: 4 weeks ]
    Changes in fasting glucose (mmol/L)


Secondary Outcome Measures :
  1. Intestinal microbiota composition [ Time Frame: 4 weeks ]
    Changes from baseline of relative abundance (%) of bacterial phyla, genera and species between groups and within participants.

  2. Immunologic profile [ Time Frame: 6 weeks ]
    Absolute counts of different immunologic cell types using Cytometry by time of flight (CyTOF) mass cytometry at baseline, 4 weeks and 6 weeks.

  3. 6-BT pharmacokinetics [ Time Frame: 6-BT pharmacokinetics as described above will be performed at baseline and after 4 weeks. ]
    Quantitatively measuring plasma concentrations of 6-BT at -15, 30, 60, 90, 120, 240 and 300 minutes following 6-BT capsule ingestion

  4. Hepatic stiffness [ Time Frame: 0 and 4 weeks ]
    Hepatic stiffness will be determined non-invasively by MRI using a special hepatic scanning protocol of 30 minutes

  5. Hepatic fat content [ Time Frame: 0 and 4 weeks ]
    Hepatic fat content will be determined non-invasively by MRI using a special hepatic scanning protocol of 30 minutes

  6. Dietary intake [ Time Frame: 4 weeks ]
    Participants are asked to fill out an online dietary questionnaire for the 3 days prior to study visit 2,3,4,5 and 7

  7. Low-density lipoprotein (LDL) [ Time Frame: 4 weeks ]
    Changes in LDL (mmol/L)

  8. High-density lipoprotein (HDL) [ Time Frame: 4 weeks ]
    Changes in HDL (mmol/L)

  9. Triglycerides [ Time Frame: 4 weeks ]
    Changes in triglycerides (mmol/L)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   35 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

• 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/
  • blood pressure ≥130/85 mm Hg.

AND/ OR Homeostatic Model Assessment for 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
  • Exclusion criterion for MRI liver (see E4_BROMO_vragenlijst MRI)
  • Alcohol abuse

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05971524


Contacts
Layout table for location contacts
Contact: Nordin MJ Hanssen, dr. 020-56691111 n.m.j.hanssen@amsterdamumc.nl

Locations
Layout table for location information
Netherlands
Amsterdam UMC Recruiting
Amsterdam, Noord-Holland, Netherlands, 1105AZ
Contact: N Hanssen, dr    020-5669111    n.m.j.hanssen@amsterdamumc.nl   
Sponsors and Collaborators
Nordin Hanssen
Investigators
Layout table for investigator information
Principal Investigator: Nordin MJ Hanssen, dr. Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Layout table for additonal information
Responsible Party: Nordin Hanssen, Principal Investigator, Amsterdam University Medical Centers (UMC), Location Academic Medical Center (AMC)
ClinicalTrials.gov Identifier: NCT05971524    
Other Study ID Numbers: NL83061.018.22
First Posted: August 2, 2023    Key Record Dates
Last Update Posted: August 22, 2023
Last Verified: August 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Metabolic Syndrome
Syndrome
Disease
Pathologic Processes
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases