Effect of Weight Loss on Brain Insulin Sensitivity in Humans
Primary Purpose
Insulin Resistance
Status
Recruiting
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
nasal insulin
placebo spray
Sponsored by
About this trial
This is an interventional basic science trial for Insulin Resistance
Eligibility Criteria
Inclusion Criteria:
- HbA1c <6.5%
- Age between 40 and 75 years
- No intake of antidiabetic drugs or drugs for weight reduction
- no steroid intake
- Stable medication over 10 weeks before the start of the study
Exclusion Criteria:
- Persons who wear non-removable metal parts in or on the body.
- Persons with reduced temperature sensitivity and / or increased sensitivity to heating of the body
- Cardiovascular disease can not be ruled out, e.g. manifest coronary heart disease, heart failure greater than NYHA 2, previous heart attack, stroke condition
- Persons with hearing impairment or increased sensitivity to loud noises
- People with claustrophobia
- Minors or non-consenting subjects are also excluded
- Subjects with an operation less than 3 months
- Simultaneous participation in other studies
- Neurological and psychiatric disorders
- Subjects with hemoglobin Hb <11 g / dl
- Hypersensitivity to any of the substances used
Sites / Locations
- University of Tuebingen, Department of Internal Medicine IVRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
nasal insulin
placebo spray
Arm Description
daily administration of 160 U of human insulin as nasal spray
daily administration of placebo solution as nasal spray
Outcomes
Primary Outcome Measures
brain insulin sensitivity
fMRI measurement will be performed before and after administration of 160 U of human insulin as nasal spray. Changes in regional activity will be quantified to assess regional brain insulin sensitivity.
Secondary Outcome Measures
Effect of daily administration of 160 U nasal insulin or placebo over 8 weeks on body weight.
Participants will receive nasal insulin or placebo in a double-blind randomized fashion. Before and after 8 weeks body weight will be recorded.
Effect of daily administration of 160 U nasal insulin or placebo over 8 weeks on glucose tolerance .
Participants will receive nasal insulin or placebo in a double-blind randomized fashion. Before and after 8 weeks glucose tolerance will be assessed using a 75 g oral glucose tolerance test.
Effect of daily administration of 160 U nasal insulin or placebo over 8 weeks on body composition .
Participants will receive nasal insulin or placebo in a double-blind randomized fashion. Before and after 8 weeks body composition will be addressed by whole-body MRI and liver MRS.
whole-body insulin sensitivity
Insulin sensitivity will be estimated from a frequent-sampling 75 g oral glucose tolerance test using the Matsuda formula.
Glucose tolerance
a 75 g oral glucose tolerance test will be performed. Glucose tolerance will be defined by the American Diabetes Association criteria.
Cognitive function
cognitive function will be addressed by neuropsychological testing.
Full Information
NCT ID
NCT02991365
First Posted
December 1, 2016
Last Updated
March 25, 2022
Sponsor
University Hospital Tuebingen
1. Study Identification
Unique Protocol Identification Number
NCT02991365
Brief Title
Effect of Weight Loss on Brain Insulin Sensitivity in Humans
Official Title
Effekt Von Gewichtsabnahme Auf Die zentralnervöse Insulinresistenz Des Menschen
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 2016 (Actual)
Primary Completion Date
December 2022 (Anticipated)
Study Completion Date
March 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital Tuebingen
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Obesity if known to be associated with brain insulin resistance in humans. This condition has not only implication for the brain but also for whole-body energy homeostasis. Research in rodents indicates that weight loss is able to improve insulin sensitivity of the brain. The current project will test this hypothesis in humans. Therefore, brain insulin sensitivity will be assessed by fMRI in combination with intranasal insulin administration, using an established protocol. Furthermore, effects of daily administration of insulin nasal spray (versus placebo) over 8 weeks will be assessed as secondary (exploratory) variables.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Insulin Resistance
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
nasal insulin
Arm Type
Active Comparator
Arm Description
daily administration of 160 U of human insulin as nasal spray
Arm Title
placebo spray
Arm Type
Placebo Comparator
Arm Description
daily administration of placebo solution as nasal spray
Intervention Type
Other
Intervention Name(s)
nasal insulin
Intervention Type
Other
Intervention Name(s)
placebo spray
Primary Outcome Measure Information:
Title
brain insulin sensitivity
Description
fMRI measurement will be performed before and after administration of 160 U of human insulin as nasal spray. Changes in regional activity will be quantified to assess regional brain insulin sensitivity.
Time Frame
30 minutes after administration of nasal insulin
Secondary Outcome Measure Information:
Title
Effect of daily administration of 160 U nasal insulin or placebo over 8 weeks on body weight.
Description
Participants will receive nasal insulin or placebo in a double-blind randomized fashion. Before and after 8 weeks body weight will be recorded.
Time Frame
8 weeks
Title
Effect of daily administration of 160 U nasal insulin or placebo over 8 weeks on glucose tolerance .
Description
Participants will receive nasal insulin or placebo in a double-blind randomized fashion. Before and after 8 weeks glucose tolerance will be assessed using a 75 g oral glucose tolerance test.
Time Frame
8 weeks
Title
Effect of daily administration of 160 U nasal insulin or placebo over 8 weeks on body composition .
Description
Participants will receive nasal insulin or placebo in a double-blind randomized fashion. Before and after 8 weeks body composition will be addressed by whole-body MRI and liver MRS.
Time Frame
8 weeks
Title
whole-body insulin sensitivity
Description
Insulin sensitivity will be estimated from a frequent-sampling 75 g oral glucose tolerance test using the Matsuda formula.
Time Frame
2 hours
Title
Glucose tolerance
Description
a 75 g oral glucose tolerance test will be performed. Glucose tolerance will be defined by the American Diabetes Association criteria.
Time Frame
2 hours
Title
Cognitive function
Description
cognitive function will be addressed by neuropsychological testing.
Time Frame
1 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
HbA1c <6.5%
Age between 40 and 75 years
No intake of antidiabetic drugs or drugs for weight reduction
no steroid intake
Stable medication over 10 weeks before the start of the study
Exclusion Criteria:
Persons who wear non-removable metal parts in or on the body.
Persons with reduced temperature sensitivity and / or increased sensitivity to heating of the body
Cardiovascular disease can not be ruled out, e.g. manifest coronary heart disease, heart failure greater than NYHA 2, previous heart attack, stroke condition
Persons with hearing impairment or increased sensitivity to loud noises
People with claustrophobia
Minors or non-consenting subjects are also excluded
Subjects with an operation less than 3 months
Simultaneous participation in other studies
Neurological and psychiatric disorders
Subjects with hemoglobin Hb <11 g / dl
Hypersensitivity to any of the substances used
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Andreas Fritsche, MD
Phone
+49 7071 29 80687
Email
andreas.fritsche@med.uni-tuebingen.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andreas Fritsche, MD
Organizational Affiliation
University of Tübingen Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Tuebingen, Department of Internal Medicine IV
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andreas Fritsche, Prof. Dr.
Phone
+49 7071 29 82714
Email
andreas.fritsche@med.uni-tuebingen.de
First Name & Middle Initial & Last Name & Degree
Martin Heni, Dr.
Phone
+49 7071 29 82714
Email
martin.heni@med.uni-tuebingen.de
First Name & Middle Initial & Last Name & Degree
Martin Heni, MD
12. IPD Sharing Statement
Plan to Share IPD
No
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Effect of Weight Loss on Brain Insulin Sensitivity in Humans
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