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Central Insulin Sensitivity in Individuals With Type 2 Diabetes (T2D) and at Risk for Developing T2D

Primary Purpose

Central Insulin Resistance, Diabetes Mellitus, Type 2, PreDiabetes

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Human nasal insulin
Placebo
Sponsored by
University Hospital Tuebingen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Central Insulin Resistance

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: manifest diabetes mellitus type 2 with initial diagnosis ≤ 10 years ago, defined as a fasting blood glucose greater than 126 mg/dl and/or a blood glucose greater than 200 mg/dl at the 120 minute time point in the oral glucose tolerance test with 75 g glucose and/or an HbA1c greater than 6.5% or a currently existing increased risk of developing type 2 diabetes, defined as prediabetes, defined as elevated fasting blood glucose (IFG), fasting blood glucose between 100 and 125 mg/dl) and/or impaired glucose tolerance (IGT), 120-minute oral glucose tolerance test blood glucose between 140 and 199 mg/dl) and/or HbA1c between 5.7% and 6.4% with and/or at least one of the following factors indicating an increased risk for developing type 2 diabetes mellitus: previously existing prediabetes and/or recent-onset gestational diabetes, and/or positive family history (1st degree family members) for type 2 diabetes mellitus and/or BMI greater than 27 kg/m2 or no manifest diabetes mellitus type 2 and no currently existing increased risk for developing type 2 diabetes (control group: BMI 18.5 to 24.5 kg/m2) female and male (1:1), voluntary adults at least 18 years old and able to give consent understanding of study explanations and instructions consent to information in case of unexpected proven pathological findings. Exclusion Criteria: Only in subjects without manifest diabetes mellitus type 2: Taking medications that affect sugar metabolism (e.g., antidiabetic medications or glucocorticoids). Diabetes mellitus type 1 or Latent autoimmune diabetes in the adult (GAD and/or IA2 antibodies positive) MODY (Maturity onset Diabetes of the Young) Decompensated diabetes mellitus type 2 (HbA1c greater than 9.6% and/or fasting blood glucose > 230 mg/dl) BMI < 18.5 or > 45 kg/m2 Individuals wearing non-removable metal devices in or on the body such as: pacemakers artificial heart valves metal prostheses implanted magnetic metal parts (screws, plates from surgery) coils metal splinters/garnet chips fixed braces retainers going over more than four teeth acupuncture needle Insulin pump intraport Tattoos, eye shadow, etc. there is a pregnancy or pregnancy cannot be excluded breastfeeding women Individuals with impaired temperature sensation and/or increased sensitivity to heating of the body. symptomatic coronary heart disease, heart failure greater than NYHA 3, previous heart attack Condition following stroke Individuals with hearing disease or increased sensitivity to loud sounds Persons with claustrophobia (fear of place) Minors or subjects incapable of giving consent Subjects who have had an operation less than 3 months ago Acute illness or infection within the last 4 weeks Severe neurological or psychiatric diseases, e.g. severe depression (at least 29 points according to BDI II), schizophrenia or bipolar disorder. Use of centrally acting drugs Known presence of malignant disease within the last 5 years Diseases of the pancreas Systemic infection (CRP > 1 mg/dl) Following bariatric surgery Antibiotic therapy within the last 4 weeks prior to study inclusion No consent to be informed about incidentally discovered pathological findings Participation in interventional trials and receipt of investigational medication in the last 30 days Severe diabetic complications such as chronic kidney disease (KDIGO CKD greater than G4) or severe proliferative retinopathy Subjects with hemoglobin levels Hb<10.5g/dl (for women), Hb<11.5g/dl (for men) Other medical conditions that, in the opinion of an investigator, may jeopardize the success of the study or indicate that the subject may be at risk of harm Allergic diseases to any of the substances used

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Placebo Comparator

    Arm Label

    Nasal insulin spray

    Placebo spray

    Arm Description

    Outcomes

    Primary Outcome Measures

    Comparison of brain insulin sensitivity in different age, weight, sex and metabolic risk groups
    fMRI measurement will be performed before and after administration of 160 U human insulin or placebo as nasal spray. Changes in regional brain activity will be quantified by cerebral blood flow and blood oxygenation dependent (BOLD) signal to assess regional brain insulin sensitivity. Brain insulin sensitivity will be compared between 5 groups (T2DM-high risk group, T2DM-low risk group, elevated risk for developing T2DM-high risk group, elevated risk for developing T2DM-low risk group, lean and healthy group). Persons are categorized into normal weight and overweight/obese based on the Body Mass Index (BMI). Age groups are build based on a median split. Metabolic risk groups are build based on Ahlqvist-criteria (T2DM) and based on Wagner-criteria (elevated risk for developing T2DM).
    Comparison of cognitive function between subtype clusters of different metabolic groups (increased risk for developing manifest type 2 diabetes cluster, manifest type 2 diabetes cluster)
    CANTAB test will be performed
    Comparison of the blood-brain-barrier permeability in different age, weight, sex and metabolic risk groups
    fMRI measurement will be performed before and after administration of 160 U human insulin or placebo as nasal spray. Changes in blood-brain-barrier permeability will be quantified by cerebral blood flow and blood oxygenation dependent (BOLD) signal to assess blood-brain-barrier permeability. blood-brain-barrier permeability will be compared between 5 groups (T2DM-high risk group, T2DM-low risk group, elevated risk for developing T2DM-high risk group, elevated risk for developing T2DM-low risk group, lean and healthy group). Persons are categorized into normal weight and overweight/obese based on the Body Mass Index (BMI). Age groups are build based on a median split. Metabolic risk groups are build based on Ahlqvist-criteria (T2DM) and based on Wagner-criteria (elevated risk for developing T2DM).

    Secondary Outcome Measures

    Full Information

    First Posted
    March 21, 2023
    Last Updated
    May 12, 2023
    Sponsor
    University Hospital Tuebingen
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05856877
    Brief Title
    Central Insulin Sensitivity in Individuals With Type 2 Diabetes (T2D) and at Risk for Developing T2D
    Official Title
    Zentrale Insulinsensitivität Bei Personen Mit Typ-2-Diabetes Sowie Bei Personen Mit erhöhtem Risiko für Die Entwicklung Von Typ-2-Diabetes
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    May 8, 2023 (Anticipated)
    Primary Completion Date
    May 31, 2025 (Anticipated)
    Study Completion Date
    December 31, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    University Hospital Tuebingen

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    Beside well described peripheral effects, insulin can also affect the human central nervous system. Centrally acting insulin seems to have an influence e.g. on whole-body metabolism and food intake. Targeting insulin receptors in the central nervous system can modulate peripheral insulin sensitivity as well as pancreatic insulin secretion. In humans, the effect of insulin can be measured in different brain areas as estimate of central nervous insulin sensitivity. Reduced central nervous insulin sensitivity, called "central insulin resistance," has been associated, for example, with obesity, unfavorable body fat distribution, and impaired cognitive functionality. Recently novel subtypes and risk clusters of diabetes and prediabetes have been identified. In this study the investigators want to investigate and compare central nervous insulin sensitivity as well as cognitive function in the different diabetes and prediabetes risk clusters.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Central Insulin Resistance, Diabetes Mellitus, Type 2, PreDiabetes

    7. Study Design

    Primary Purpose
    Basic Science
    Study Phase
    Not Applicable
    Interventional Study Model
    Crossover Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    180 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Nasal insulin spray
    Arm Type
    Active Comparator
    Arm Title
    Placebo spray
    Arm Type
    Placebo Comparator
    Intervention Type
    Other
    Intervention Name(s)
    Human nasal insulin
    Intervention Description
    single dose of 160 U of human insulin as nasal spray
    Intervention Type
    Other
    Intervention Name(s)
    Placebo
    Intervention Description
    Single dose of placebo solution as nasal spray
    Primary Outcome Measure Information:
    Title
    Comparison of brain insulin sensitivity in different age, weight, sex and metabolic risk groups
    Description
    fMRI measurement will be performed before and after administration of 160 U human insulin or placebo as nasal spray. Changes in regional brain activity will be quantified by cerebral blood flow and blood oxygenation dependent (BOLD) signal to assess regional brain insulin sensitivity. Brain insulin sensitivity will be compared between 5 groups (T2DM-high risk group, T2DM-low risk group, elevated risk for developing T2DM-high risk group, elevated risk for developing T2DM-low risk group, lean and healthy group). Persons are categorized into normal weight and overweight/obese based on the Body Mass Index (BMI). Age groups are build based on a median split. Metabolic risk groups are build based on Ahlqvist-criteria (T2DM) and based on Wagner-criteria (elevated risk for developing T2DM).
    Time Frame
    30 minutes after Administration of nasal insulin
    Title
    Comparison of cognitive function between subtype clusters of different metabolic groups (increased risk for developing manifest type 2 diabetes cluster, manifest type 2 diabetes cluster)
    Description
    CANTAB test will be performed
    Time Frame
    45 minutes
    Title
    Comparison of the blood-brain-barrier permeability in different age, weight, sex and metabolic risk groups
    Description
    fMRI measurement will be performed before and after administration of 160 U human insulin or placebo as nasal spray. Changes in blood-brain-barrier permeability will be quantified by cerebral blood flow and blood oxygenation dependent (BOLD) signal to assess blood-brain-barrier permeability. blood-brain-barrier permeability will be compared between 5 groups (T2DM-high risk group, T2DM-low risk group, elevated risk for developing T2DM-high risk group, elevated risk for developing T2DM-low risk group, lean and healthy group). Persons are categorized into normal weight and overweight/obese based on the Body Mass Index (BMI). Age groups are build based on a median split. Metabolic risk groups are build based on Ahlqvist-criteria (T2DM) and based on Wagner-criteria (elevated risk for developing T2DM).
    Time Frame
    30 minutes after Administration of nasal insulin

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: manifest diabetes mellitus type 2 with initial diagnosis ≤ 10 years ago, defined as a fasting blood glucose greater than 126 mg/dl and/or a blood glucose greater than 200 mg/dl at the 120 minute time point in the oral glucose tolerance test with 75 g glucose and/or an HbA1c greater than 6.5% or a currently existing increased risk of developing type 2 diabetes, defined as prediabetes, defined as elevated fasting blood glucose (IFG), fasting blood glucose between 100 and 125 mg/dl) and/or impaired glucose tolerance (IGT), 120-minute oral glucose tolerance test blood glucose between 140 and 199 mg/dl) and/or HbA1c between 5.7% and 6.4% with and/or at least one of the following factors indicating an increased risk for developing type 2 diabetes mellitus: previously existing prediabetes and/or recent-onset gestational diabetes, and/or positive family history (1st degree family members) for type 2 diabetes mellitus and/or BMI greater than 27 kg/m2 or no manifest diabetes mellitus type 2 and no currently existing increased risk for developing type 2 diabetes (control group: BMI 18.5 to 24.5 kg/m2) female and male (1:1), voluntary adults at least 18 years old and able to give consent understanding of study explanations and instructions consent to information in case of unexpected proven pathological findings. Exclusion Criteria: Only in subjects without manifest diabetes mellitus type 2: Taking medications that affect sugar metabolism (e.g., antidiabetic medications or glucocorticoids). Diabetes mellitus type 1 or Latent autoimmune diabetes in the adult (GAD and/or IA2 antibodies positive) MODY (Maturity onset Diabetes of the Young) Decompensated diabetes mellitus type 2 (HbA1c greater than 9.6% and/or fasting blood glucose > 230 mg/dl) BMI < 18.5 or > 45 kg/m2 Individuals wearing non-removable metal devices in or on the body such as: pacemakers artificial heart valves metal prostheses implanted magnetic metal parts (screws, plates from surgery) coils metal splinters/garnet chips fixed braces retainers going over more than four teeth acupuncture needle Insulin pump intraport Tattoos, eye shadow, etc. there is a pregnancy or pregnancy cannot be excluded breastfeeding women Individuals with impaired temperature sensation and/or increased sensitivity to heating of the body. symptomatic coronary heart disease, heart failure greater than NYHA 3, previous heart attack Condition following stroke Individuals with hearing disease or increased sensitivity to loud sounds Persons with claustrophobia (fear of place) Minors or subjects incapable of giving consent Subjects who have had an operation less than 3 months ago Acute illness or infection within the last 4 weeks Severe neurological or psychiatric diseases, e.g. severe depression (at least 29 points according to BDI II), schizophrenia or bipolar disorder. Use of centrally acting drugs Known presence of malignant disease within the last 5 years Diseases of the pancreas Systemic infection (CRP > 1 mg/dl) Following bariatric surgery Antibiotic therapy within the last 4 weeks prior to study inclusion No consent to be informed about incidentally discovered pathological findings Participation in interventional trials and receipt of investigational medication in the last 30 days Severe diabetic complications such as chronic kidney disease (KDIGO CKD greater than G4) or severe proliferative retinopathy Subjects with hemoglobin levels Hb<10.5g/dl (for women), Hb<11.5g/dl (for men) Other medical conditions that, in the opinion of an investigator, may jeopardize the success of the study or indicate that the subject may be at risk of harm Allergic diseases to any of the substances used
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Stephanie Kullmann, Prof.
    Phone
    070712987702
    Email
    stephanie.kullmann@med.uni-tuebingen.de
    First Name & Middle Initial & Last Name or Official Title & Degree
    Christian Kübler, Dr.
    Phone
    070712968784
    Email
    christian.kuebler@med.uni-tuebingen.de

    12. IPD Sharing Statement

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    Central Insulin Sensitivity in Individuals With Type 2 Diabetes (T2D) and at Risk for Developing T2D

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