BREBAD study
Effect of oral 6-Bromotryptophan vs placebo on REsidual Beta-cell function and Autoimmunity in people with new-onset type 1 diabetes (2026)
Background and Rationale
Despite continuous advancements in type 1 diabetes (T1D) management and the development of glucose-monitoring and insulin-administering devices, T1D remains a high-burden disease with a high risk of comorbidities and a negative impact ont he quality of life of people with type 1 diabetes (PWDs). After diagnosis, newly diagnosed PWDs rapidly lose their ability to produce insulin in the first five years, after which any remaining residual beta-cell function tends to stabilize. Preserving residual beta-cell function is associated with better glycaemic control and fewer long-term complications, making it a clinically meaningful therapeutic target.
Increasing evidence points toward the gut microbiome as a key modulator of metabolic and immune pathways relevant to T1D progression. Commensal gut microbes constantly engage in communication with the immune system through the production of metabolites that, once absorbed into the circulation, act as signalling molecules in the host. In this context, we recently identified 6-bromotryptophan (6-BT), a novel bacterially derived metabolite of the essential amino acid tryptophan, whose plasma levels are reduced in both newly diagnosed and people with long-standing T1D compared to healthy controls. Higher plasma 6-BT levels correlate with preserved residual beta-cell function and are negatively associated with inflammatory markers such as circulating CD8 T cell counts. In preclinical models, 6-BT exerted anti-inflammatory effects on immune cells, stimulated insulin secretion by beta cells, limited insulitis, and expanded immunosuppressive regulatory T cells. A first-in-human safety and dose-finding trial confirmed that daily oral supplementation with 8 mg 6-BT is safe, well-tolerated, and effectively raises plasma 6-BT levels, with a concomitant beneficial effect on postprandial glucose metabolism.
Study Objectives
The BREBAD study aims to investigate whether:
- Oral supplementation with 6-BT can preserve residual beta-cell function, as measured by stimulated C-peptide during a mixed-meal test, in newly diagnosed PWDs
- 6-BT intake can improve glycaemic control, reflected by longer time-in-range and reduced exogenous insulin requirements
- 6-BT supplementation limits aberrant immune responses and autoimmunity characteristic of T1D, including changes in circulating T cell subsets and autoreactive T cell frequencies
- Long-term treatment with 6-BT affects gut microbiota composition and the plasma metabolome, and whether any effects persist after treatment cessation
Study Design & Study Population
BREBAD is a phase II, double-blind, placebo-controlled randomised clinical trial in 34 adults with newly diagnosed T1D. Participants are randomised 1:1 to receive either 8 mg 6-BT or placebo once daily as oral gelatin capsules for 12 months, followed by a 6-month washout period, with a final study visit at 18 months.
The study includes adults aged 18–30 years with a T1D diagnosis no more than 6 months prior to enrolment, detectable residual beta-cell function, seropositivity for at least one beta-cell autoantibody, and a BMI between 18 and 30 kg/m². Participants are recruited through Amsterdam UMC (location AMC) and Diabeter Centrum Amsterdam.
Study Procedures and Data Collection
At each of the six study visits (months 0, 1, 3, 6, 12, and 18), the following assessments are performed:
- A standardised 2-hour mixed-meal test with serial blood sampling to assess stimulated C-peptide and glucose excursions
- Blood and urine samples for safety parameters, inflammatory markers, and 6-BT concentration measurements
- Stool samples for gut microbiome analysis by shotgun metagenomics
- Continuous glucose monitoring (CGM) data extraction for time-in-range analysis
- Isolation of peripheral blood mononuclear cells (PBMCs) for detailed immunophenotyping
- Dietary assessment using an online food diary
Each study visit takes approximately 4 hours. Participants remain under the care of their own treating physician throughout; study visits are additional to routine diabetes care. Participants receive a reimbursement of €350 plus travel costs for full study participation.
Inquiries about this study can be sent to j.dengerink@amsterdamumc.nl or research@diabetercentrumamsterdam.nl