Ignite Creation Date:
2025-12-25 @ 2:05 AM
Ignite Modification Date:
2025-12-26 @ 12:30 AM
Study NCT ID:
NCT06560060
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-08-19
First Post:
2024-08-15
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Do People With Complications of Type 1 Diabetes Mellitus Have a Different Microbiome (MARVEL)
Sponsor:
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Organization:
Study Overview
Official Title:
Is the Gut Microbiome Associated With Residual Β-Cell Function and DeVElopment of Complications in Individuals With Longstanding Type 1 Diabetes Mellitus (MARVEL)
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MARVEL
Brief Summary:
This study looks at whether people with type 1 diabetes have different gut bacteria. We also want to see if this is linked to keeping insulin production up and preventing complications like heart disease and nerve damage. The aim is to find ways to keep more of the functions working, avoid low blood sugar and reduce diabetes complications.
Detailed Description:
Rationale: It has become apparent that most individuals with type 1 diabetes mellitus (T1D) have some remaining β-cell function. Individuals with T1D and a preserved β-cell function have a lower risk of hypoglycemia and diabetic complications. The factors regulating residual β-cell function are unknown. A likely mechanism leading to β-cell preservation is regulation of immunological tone by the gut microbiome. Recently we published in a small pilot cohort (GUTDM1, METC 2020\_105) that residual β-cell function is linked to better glycemic control (time in range) and linked to specific gut microbiota composition. Since this cohort was too small to also show a link with presence of diabetic complications and recruit enough individuals with preserved β-cell function for confirmatory intervention trials to increase β-cell function, we will now aim to recruit a larger follow-up cohort. The aim of this cohort is to a) investigate whether residual β-cell function is associated with gut microbiome composition and circulating immune cell counts in individuals with T1D and diabetic complications b) identify 500 potential eligible individuals with preserved β-cell function for future intervention trials.
Objective:
1. To investigate whether T1D individuals with preserved β-cell function exhibit a distinct gut microbial and circulating immune cell signature, leading to a reduced incidence of diabetes complications (CVD, nephropathy, neuropathy, and retinopathy).
2. Identify individuals with preserved β-cell function for diagnostics as well as future intervention studies to increase β-cell function.
Study design: 10-year longitudinal observational multicenter cohort study
Study population: 5000 individuals with type 1 diabetes \>18 years of age, visiting the outpatient clinic of Diabeter center Amsterdam and Diabeter Nederland.
Main study parameters/endpoints: The primary endpoint is long-term residual β-cell function as assessed by baseline and stimulated 2-hour post meal urinary C-peptide levels at 3,6 and 10 years follow-up. The secondary endpoint pertains presence and incidence of diabetes complications (cardiovascular disease, nephropathy, neuropathy and retinopathy), gut microbiota composition measured in feces with shotgun sequencing, glucose time-in-range (CGM-metrics) and subsequent exogenous insulin dose. Tertiary endpoints include the profiling of immune cell subsets, assessment of autoreactive T lymphocytes and HLA typing by high resolution sequencing of circulating leukocytes (IMMOCHIP) in relation to untargeted plasma metabolomics (Metabolon).
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: This study is considered a negligible-risk study. The patient will complete several questionnaires, keep track of a food diary and collect urine and feces prior to the baseline study visit. At the study visit we will require a fasted plasma sample, this will slightly increase the chances of a hypoglycemic episode, largely mitigated because all participants carry a continues glucose monitor. Additionally, we will calculate BMI, waist circumference, liver stiffness and measure blood pressure. The questionnaires inquire about the burden of diabetic complications, socio-economic status and financial literacy, abdominal complaints and hypoglycemic episodes, and comorbidities associated with diabetes, quality of life and psychological functioning. We argue that the risk and discomfort associated with this study is similar to the yearly diabetes check-up and justified in light of the potentially profound insights and novel treatments to be gained by studying the impact of the gut microbiome on residual β-cell function in T1D.
Objective:
1. To investigate whether T1D individuals with preserved β-cell function exhibit a distinct gut microbial and circulating immune cell signature, leading to a reduced incidence of diabetes complications (CVD, nephropathy, neuropathy, and retinopathy).
2. Identify individuals with preserved β-cell function for diagnostics as well as future intervention studies to increase β-cell function.
Study design: 10-year longitudinal observational multicenter cohort study
Study population: 5000 individuals with type 1 diabetes \>18 years of age, visiting the outpatient clinic of Diabeter center Amsterdam and Diabeter Nederland.
Main study parameters/endpoints: The primary endpoint is long-term residual β-cell function as assessed by baseline and stimulated 2-hour post meal urinary C-peptide levels at 3,6 and 10 years follow-up. The secondary endpoint pertains presence and incidence of diabetes complications (cardiovascular disease, nephropathy, neuropathy and retinopathy), gut microbiota composition measured in feces with shotgun sequencing, glucose time-in-range (CGM-metrics) and subsequent exogenous insulin dose. Tertiary endpoints include the profiling of immune cell subsets, assessment of autoreactive T lymphocytes and HLA typing by high resolution sequencing of circulating leukocytes (IMMOCHIP) in relation to untargeted plasma metabolomics (Metabolon).
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: This study is considered a negligible-risk study. The patient will complete several questionnaires, keep track of a food diary and collect urine and feces prior to the baseline study visit. At the study visit we will require a fasted plasma sample, this will slightly increase the chances of a hypoglycemic episode, largely mitigated because all participants carry a continues glucose monitor. Additionally, we will calculate BMI, waist circumference, liver stiffness and measure blood pressure. The questionnaires inquire about the burden of diabetic complications, socio-economic status and financial literacy, abdominal complaints and hypoglycemic episodes, and comorbidities associated with diabetes, quality of life and psychological functioning. We argue that the risk and discomfort associated with this study is similar to the yearly diabetes check-up and justified in light of the potentially profound insights and novel treatments to be gained by studying the impact of the gut microbiome on residual β-cell function in T1D.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: