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出境医 / 临床实验 / "Effect of Central Insulin Administration on Whole-body Insulin Sensitivity in Women"

"Effect of Central Insulin Administration on Whole-body Insulin Sensitivity in Women"

Study Description
Brief Summary:

The human brain is an insulin sensitive organ. Brain insulin action modulates peripheral insulin sensitivity in young lean men. As a underlying mechanism, the investigators previously detected suppression of endogenous glucose production and stimulation of glucose disappearance to peripheral tissue in response to brain insulin delivery by nasal spray. Whether this holds true in young woman is unknown, since differences in brain insulin response between sexes have been reported. The investigators will address this question by combining the delivery of insulin to the brain as nasal spray with hyperinsulinemic euglycemic clamp experiments in natural cycling women.

In the planned randomized, placebo controlled cross-over study, female participants will undergo four hyperinsulinemic euglycemic experiments with tracer dilution, two in the first phase and two in the second phase of their menstrual cycle. On one of the study days per menstrual phase, subjects will receive intranasal insulin administration, on the other placebo spray. The protocol has been successfully applied previously in men. Based on the results of this trial, the investigators calculated a required sample size of N=10 for the planned study in women.

These experiments will help to better understand the role of brain insulin action in a broader sense. The results can be the basis for larger clinical trials that address the sex-specific impact of brain insulin resistance for glucose metabolism and diabetes risk.


Condition or disease Intervention/treatment Phase
Insulin Sensitivity Drug: intranasal insulin Drug: Placebo spray Not Applicable

Detailed Description:

"Effect of central insulin administration on whole-body insulin sensitivity in women" The human brain is an insulin sensitive organ. Brain insulin action modulates peripheral insulin sensitivity in young lean men. As a underlying mechanism, the investigators previously detected suppression of endogenous glucose production and stimulation of glucose disappearance to peripheral tissue in response to brain insulin delivery by nasal spray. Whether this holds true in young woman is unknown, since differences in brain insulin response between sexes have been reported. The investigators will address this question by combining the delivery of insulin to the brain as nasal spray with hyperinsulinemic euglycemic clamp experiments in natural cycling women.

In the planned randomized, placebo controlled cross-over study, female participants will undergo four hyperinsulinemic euglycemic experiments with tracer dilution, two in the first phase and two in the second phase of their menstrual cycle. On one of the study days per menstrual phase, subjects will receive intranasal insulin administration, on the other placebo spray. The protocol has been successfully applied previously in men. Based on the results of this trial, the investigators calculated a required sample size of N=10 for the planned study in women.

These experiments will help to better understand the role of brain insulin action in a broader sense. The results can be the basis for larger clinical trials that address the sex-specific impact of brain insulin resistance for glucose metabolism and diabetes risk.

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Basic Science
Official Title: "Effect of Central Insulin Administration on Whole-body Insulin Sensitivity in Women"
Actual Study Start Date : April 21, 2019
Estimated Primary Completion Date : July 31, 2021
Estimated Study Completion Date : August 31, 2021
Arms and Interventions
Arm Intervention/treatment
Active Comparator: Insulin nasal spray
160 Units of human insulin as nasal spray
Drug: intranasal insulin
application of 160 units human insulin

Placebo Comparator: Placebo nasal spray
Nasal spray containing placebo solution
Drug: Placebo spray
nasal spray containing placebo solution

Outcome Measures
Primary Outcome Measures :
  1. Change in the peripheral insulin sensitivity [ Time Frame: 60-90 minutes and 150-210 minutes during euglycemic clamp ]
    Effect of nasal insulin versus placebo on peripheral insulin sensitivity assessed by euglycemic hyperinsulinemic clamp.


Secondary Outcome Measures :
  1. Correlation with autonomous nervous system activity [ Time Frame: 70-80 minutes and 190-200 minutes during euglycemic clamp ]
    Correlation of the change in peripheral insulin sensitivity by central insulin action with the simultaneous change of the autonomous nervous system (measured by heart rate variability).

  2. Differential effects dependent on female sexual hormones [ Time Frame: 60-90 minutes and 150-210 minutes during euglycemic clamp ]
    Correlation of the change in peripheral insulin sensitivity by central insulin action dependent on the time point in menstrual cycle

  3. Effect of menstrual cycle on insulin sensitivity before spray application [ Time Frame: 60-90minutes ]
    Will be measured by hyperinsulinemic euglycemic clamp

  4. Effect of menstrual cycle on brain insulin sensitivity [ Time Frame: 60-90 minutes ]
    Brain insulin sensitivity will be assessed by functional magnetic resonance imaging combined with intranasal insulin administration during the follicular and the luteal phase of the menstrual cycle

  5. Effect of menstrual cycle on processing of food cues in the brain [ Time Frame: 20 minutes ]
    Processing of food cues in the brain will be assessed by functional magnetic resonance imaging during the follicular and the luteal phase of the menstrual cycle


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 30 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • female volunteer adults
  • HbA1c <6.0%
  • Age between 18 and 30 years
  • Standard routine laboratory
  • No underlying diseases
  • No medication
  • No hormonal contraception
  • Understanding of the explanations of the study and the instructions

Exclusion Criteria:

  • Persons with limited temperature perception and / or increased temperature Sensitivity to warming of the body
  • Cardiovascular disease, such as manifest coronary Heart disease, heart failure greater than NYHA 2, recent myocardial infarction
  • People with a hearing disorder or increased sensitivity to loud Sounds
  • persons with claustrophobia
  • Minors or non-consenting subjects are also excluded
  • Pregnancy or breastfeeding women
  • Surgery less than 3 months ago
  • Simultaneous participation in other interventional studies
  • Acute illness or infection within the last 4 weeks
  • Neurological and psychiatric disorders
  • Subjects with hemoglobin Hb <12g / dl (at screening)
  • Allergic diseases
  • Individuals with a history of heparin-induced thrombocytopenia (HIT)
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Martin Heni 0049 7071 2982711 martin.heni@med.uni-tuebingen.de

Locations
Layout table for location information
Germany
University of Tuebingen, Department of Internal Medicine IV Recruiting
Tuebingen, Germany, 72076
Contact: Martin Heni, MD    +49 7071 29 82714    martin.heni@med.uni-tuebingen.de   
Contact: Andreas Fritsche, MD    +49 7071 29 82714    andreas.fritsche@med.uni-tuebingen.de   
Sponsors and Collaborators
University Hospital Tuebingen
Tracking Information
First Submitted Date  ICMJE April 15, 2019
First Posted Date  ICMJE April 26, 2019
Last Update Posted Date May 25, 2021
Actual Study Start Date  ICMJE April 21, 2019
Estimated Primary Completion Date July 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 25, 2019)
Change in the peripheral insulin sensitivity [ Time Frame: 60-90 minutes and 150-210 minutes during euglycemic clamp ]
Effect of nasal insulin versus placebo on peripheral insulin sensitivity assessed by euglycemic hyperinsulinemic clamp.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 20, 2021)
  • Correlation with autonomous nervous system activity [ Time Frame: 70-80 minutes and 190-200 minutes during euglycemic clamp ]
    Correlation of the change in peripheral insulin sensitivity by central insulin action with the simultaneous change of the autonomous nervous system (measured by heart rate variability).
  • Differential effects dependent on female sexual hormones [ Time Frame: 60-90 minutes and 150-210 minutes during euglycemic clamp ]
    Correlation of the change in peripheral insulin sensitivity by central insulin action dependent on the time point in menstrual cycle
  • Effect of menstrual cycle on insulin sensitivity before spray application [ Time Frame: 60-90minutes ]
    Will be measured by hyperinsulinemic euglycemic clamp
  • Effect of menstrual cycle on brain insulin sensitivity [ Time Frame: 60-90 minutes ]
    Brain insulin sensitivity will be assessed by functional magnetic resonance imaging combined with intranasal insulin administration during the follicular and the luteal phase of the menstrual cycle
  • Effect of menstrual cycle on processing of food cues in the brain [ Time Frame: 20 minutes ]
    Processing of food cues in the brain will be assessed by functional magnetic resonance imaging during the follicular and the luteal phase of the menstrual cycle
Original Secondary Outcome Measures  ICMJE
 (submitted: April 25, 2019)
  • Correlation with autonomous nervous system activity [ Time Frame: 70-80 minutes and 190-200 minutes during euglycemic clamp ]
    Correlation of the change in peripheral insulin sensitivity by central insulin action with the simultaneous change of the autonomous nervous system (measured by heart rate variability).
  • Differential effects dependent on female sexual hormones [ Time Frame: 60-90 minutes and 150-210 minutes during euglycemic clamp ]
    Correlation of the change in peripheral insulin sensitivity by central insulin action dependent on the time point in menstrual cycle
  • Effect of menstrual cycle on insulin sensitivity before spray application [ Time Frame: 60-90minutes ]
    Will be measured by hyperinsulinemic euglycemic clamp
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE "Effect of Central Insulin Administration on Whole-body Insulin Sensitivity in Women"
Official Title  ICMJE "Effect of Central Insulin Administration on Whole-body Insulin Sensitivity in Women"
Brief Summary

The human brain is an insulin sensitive organ. Brain insulin action modulates peripheral insulin sensitivity in young lean men. As a underlying mechanism, the investigators previously detected suppression of endogenous glucose production and stimulation of glucose disappearance to peripheral tissue in response to brain insulin delivery by nasal spray. Whether this holds true in young woman is unknown, since differences in brain insulin response between sexes have been reported. The investigators will address this question by combining the delivery of insulin to the brain as nasal spray with hyperinsulinemic euglycemic clamp experiments in natural cycling women.

In the planned randomized, placebo controlled cross-over study, female participants will undergo four hyperinsulinemic euglycemic experiments with tracer dilution, two in the first phase and two in the second phase of their menstrual cycle. On one of the study days per menstrual phase, subjects will receive intranasal insulin administration, on the other placebo spray. The protocol has been successfully applied previously in men. Based on the results of this trial, the investigators calculated a required sample size of N=10 for the planned study in women.

These experiments will help to better understand the role of brain insulin action in a broader sense. The results can be the basis for larger clinical trials that address the sex-specific impact of brain insulin resistance for glucose metabolism and diabetes risk.

Detailed Description

"Effect of central insulin administration on whole-body insulin sensitivity in women" The human brain is an insulin sensitive organ. Brain insulin action modulates peripheral insulin sensitivity in young lean men. As a underlying mechanism, the investigators previously detected suppression of endogenous glucose production and stimulation of glucose disappearance to peripheral tissue in response to brain insulin delivery by nasal spray. Whether this holds true in young woman is unknown, since differences in brain insulin response between sexes have been reported. The investigators will address this question by combining the delivery of insulin to the brain as nasal spray with hyperinsulinemic euglycemic clamp experiments in natural cycling women.

In the planned randomized, placebo controlled cross-over study, female participants will undergo four hyperinsulinemic euglycemic experiments with tracer dilution, two in the first phase and two in the second phase of their menstrual cycle. On one of the study days per menstrual phase, subjects will receive intranasal insulin administration, on the other placebo spray. The protocol has been successfully applied previously in men. Based on the results of this trial, the investigators calculated a required sample size of N=10 for the planned study in women.

These experiments will help to better understand the role of brain insulin action in a broader sense. The results can be the basis for larger clinical trials that address the sex-specific impact of brain insulin resistance for glucose metabolism and diabetes risk.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Basic Science
Condition  ICMJE Insulin Sensitivity
Intervention  ICMJE
  • Drug: intranasal insulin
    application of 160 units human insulin
  • Drug: Placebo spray
    nasal spray containing placebo solution
Study Arms  ICMJE
  • Active Comparator: Insulin nasal spray
    160 Units of human insulin as nasal spray
    Intervention: Drug: intranasal insulin
  • Placebo Comparator: Placebo nasal spray
    Nasal spray containing placebo solution
    Intervention: Drug: Placebo spray
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 25, 2019)
10
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 31, 2021
Estimated Primary Completion Date July 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • female volunteer adults
  • HbA1c <6.0%
  • Age between 18 and 30 years
  • Standard routine laboratory
  • No underlying diseases
  • No medication
  • No hormonal contraception
  • Understanding of the explanations of the study and the instructions

Exclusion Criteria:

  • Persons with limited temperature perception and / or increased temperature Sensitivity to warming of the body
  • Cardiovascular disease, such as manifest coronary Heart disease, heart failure greater than NYHA 2, recent myocardial infarction
  • People with a hearing disorder or increased sensitivity to loud Sounds
  • persons with claustrophobia
  • Minors or non-consenting subjects are also excluded
  • Pregnancy or breastfeeding women
  • Surgery less than 3 months ago
  • Simultaneous participation in other interventional studies
  • Acute illness or infection within the last 4 weeks
  • Neurological and psychiatric disorders
  • Subjects with hemoglobin Hb <12g / dl (at screening)
  • Allergic diseases
  • Individuals with a history of heparin-induced thrombocytopenia (HIT)
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 30 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Martin Heni 0049 7071 2982711 martin.heni@med.uni-tuebingen.de
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03929419
Other Study ID Numbers  ICMJE 568/2018BO1
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University Hospital Tuebingen
Study Sponsor  ICMJE University Hospital Tuebingen
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account University Hospital Tuebingen
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP