Effect of 4 Weeks of Oral Probiotic Desulfovibrio Piger Supplementation on Immunological and Metabolic Parameters in Individuals With Longstanding Type 1 Diabetes (PROSPER)

The goal is to establish the effect of oral probiotic Desulfovibrio piger (D. piger) supplementation on immunological and metabolic parameters in individuals with longstanding type 1 diabetes with residual beta cell function. The investigators will perform a double-blind, randomized, placebo-controlled trial in 2x10 participants to measure effects of D. piger on parameters of systemic and intestinal inflammation and residual beta cell function.

Study Overview

• Status: Recruiting
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Dietary supplement: Probiotic dietary supplement; Dietary supplement: Placebo

Detailed Description

The investigators perform a double-blind, randomized, placebo-controlled trial with two arms (10 participants per arm, total of 20 participants) in adults with longstanding type 1 diabetes with residual beta cell function. The study duration is 6 weeks, with 4 weeks of intervention in which participants will be given D. piger or placebo once daily and 2 weeks of washout period. The main study enpoints include the changes (versus baseline) in parameters of systemic/intestinal inflammation and beta cell function between the placebo and D.piger-treatment arms at the end of treatment (4 weeks). In addition, any long-lasting effects will be determined by assessing the changes in the above described markers after a 2 week washout period (6 weeks).

Secondary endpoints include glucose variability (continuous glucose monitoring, CGM), fecal microbiome composition (including strain engraftment of D. piger, plasma metabolites), immune cell phenotype and frequency and validated questionnaires (gastro-intestinal complaints) at these three timepoints (0,4,6 weeks).

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Max Nieuwdorp, Prof. Dr.; Phone Number: +31 20-5669111; Email: m.nieuwdorp@amsterdamumc.nl

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Recruiting
    • Amsterdam UMC
    • Contact: Max Nieuwdorp, Prof. Dr.; Phone Number: +31 20-5669111; Email: m.nieuwdorp@amsterdamumc.nl
  • Amsterdam, Netherlands, 1066 EC
    • Recruiting
    • Diabeter Centrum Amsterdam
    • Contact: Max Nieuwdorp, Prof. Dr.; Phone Number: +31 20-5669111; Email: m.nieuwdorp@amsterdamumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Males or females, age >18 years
• A diagnosis of type 1 diabetes, with duration of more than 5 years, with minimally one of antiGAD65, IA2, ZnT8 autoantibodies present assessed at diagnosis or routine visits at Diabeter Centrum.
• Evidence of remaining residual beta cell function with detectable UCPCR (more than 0.01 nmol/mmol C-peptide/creatinine ratio) and or fasting plasma C-peptide more than 0.2 mmol/L.
• BMI 18-30 kg/m2

Exclusion Criteria:

• Use of antibiotics or proton-pump inhibitors within the last three months before screening or during study period
• Use of other probiotic supplementation within the last month before screening or during study period
• A history of cholecystectomy
• Overt untreated gastrointestinal disease, inflammatory bowel disease or abnormal bowel habits
• Absence of a large bowel (ie colostomy)
• Evidence for comprised immunity (HIV infection, chemotherapy, other autoimmune diseases, systemic anti-inflammatory therapy)
• History of cardiovascular disaeses (CVD) events
• Hepatic enzymes>2.5 higher than the upper limit of normal range, determined during MARVEL visits/routine visits
• Kidney failure (eGFR <15ml.min/1.73m2), dialysis, kidney transplantation,
• Inability or unwillingness to donate feces or urine.
• Smoking or illicit drug use (e.g. MDMA/amphetamine/cocaine/heroin/GHB) in the past three months or use during the study period.
• Alcohol abuse (equal or above 21 units per week)
• Inability or unwillingness to provide informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probiotic Desulfovibrio piger; Probiotic bacteria D. piger (10^9 colony forming units (CFU) in 10ml PBS containing 10% glycerol and 10% maltodextrin)	Dietary supplement: Probiotic dietary supplement; Probiotic bacteria D. piger (10^9 colony forming units (CFU) in 10ml PBS containing 10% glycerol and 10% maltodextrin)
Placebo Comparator: Placebo; placebo (10ml PBS containing 10% glycerol and 10% maltodextrin)	Dietary supplement: Placebo; Placebo (10ml PBS containing 10% glycerol and 10% maltodextrin)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parameters of systemic and intestinal inflammation	systemic inflammation determined by measuring plasma CRP, and proinflammatory cytokines (IFNgamma, IFN alpha, TNFalpha) intestinal inflammation assessed by LB, iFABP, zonulin in plasma	From start treatment to the end of treatment at 4 weeks and washout at 6 weeks.
Residual beta cell function	Assessed by C peptide AUC during mixed meal tolerance test and/or post meal urine C-peptide/creatinine ratio levels.	From start treatment to the end of treatment at 4 weeks and washout at 6 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucose variability	percentage time in euglycemic range, time above range, time below range and glucose variability measured by continuous glucose monitoring (CGM)	From start treatment to the end of treatment at 4 weeks and washout at 6 weeks.
Immune cell phenotypes and frequency	Immunophenotyping by flow cytometry of PBMC (peripheral blood mononuclear cells) to determine frequency of T cell subsets with activation/exhaustion marker expression	From start treatment to the end of treatment at 4 weeks and washout at 6 weeks.
Fecal microbiome composition and strain engraftment	using 16s rRNA sequencing, primer-specific quantitative PCR for D. piger detection in feces and plasma metabolites	From start treatment to the end of treatment at 4 weeks and washout at 6 weeks.
Gastrointestinal Symptom Rating Scale (GSRS)	Questionnaire. The minimum and maximum score are 15 and 105 points respectively, and a higher score in the scale reflects more gastro-intestinal complaints.	From start treatment to the end of treatment at 4 weeks and washout at 6 weeks.

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Investigators: Principal Investigator: Max Nieuwdorp, Prof. Dr., Amsterdam UMC

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: May 5, 2026
• First Submitted That Met QC Criteria: May 10, 2026
• First Posted (Actual): May 14, 2026

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 10, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: probiotics; type 1 diabetes mellitus; gut microbiome; residual beta cell function; immunological parameters
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 1
• Other Study ID Numbers: 2025.1139

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No