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Tissue-Specific Metabolic Reprogramming in Diabetic Complications (DP3)

Primary Purpose

Type 1 Diabetes Mellitus

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Euglycemic clamp (normal blood sugar clamp) for 4 hours
hyperglycemic clamp (elevated blood sugar to 300) for 4 hours
Sponsored by
University of Michigan
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Type 1 Diabetes Mellitus

Eligibility Criteria

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

Group 1: T1DM subjects without complications:

Group 2: T1DM subjects with microalbuminuria . Group 3: T1DM subjects with advanced diabetes complications Group 4: Age-and-sex-matched healthy control subjects .

Inclusion Criteria:

General entry criteria:

Must have type 1 diabetes > 5 years duration. 18 years of age or older

Subjects in the microalbuminuria group will have a history of urinary microalbumin to creatinine ration between 30-300 m/g confirmed on repeat testing while the non-albuminuric group will have a value of less than 30 mg/g.

Subjects in advanced complications group will have confirmed Retinopathy, Peripheral and/or Autonomic Neuropathy and nephropathy.

Non diabetic individuals will be matched for age and gender and will have normal glucose tolerance, normal lipid metabolism, and normal blood pressure.

Exclusion Criteria:

Age less than 18 . Women of child-bearing potential who may be pregnant or lactating History of pancreas, kidney or liver transplant History of drug or alcohol use. History of cancer other than basal cell carcinoma or squamous cell skin cancer. Presence of a condition that in the opinion of the investigator would make it unlikely for the subject to complete the study.

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Sites / Locations

  • University of Michigan

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Type 1 Diabetes no complications.

Type 1 Diabetes with microalbuminuria

Type 1 Diabetes with advanced complications.

Aged and sex matched healthy control volunteers

Arm Description

Each cohort group will be admitted to the Michigan Clinical Research Unit for Blood glucose Clamp studies. Each subject will have a Euglycemic clamp (normal blood sugar clamp) for 4 hours and a hyperglycemic clamp (elevated blood sugar to 300) for 4 hours. Once the subject is clamped, bloods and urine will be collected to assay for specific metabolomics and proteomic biomarkers. We will perform the same clamps for each cohort.

Each cohort group will be admitted to the Michigan Clinical Research Unit for Blood glucose Clamp studies. Each subject will have a Euglycemic clamp (normal blood sugar clamp) for 4 hours and a hyperglycemic clamp (elevated blood sugar to 300) for 4 hours. Once the subject is clamped, bloods and urine will be collected to assay for specific metabolomics and proteomic biomarkers. We will perform the same clamps for each cohort.

Each cohort group will be admitted to the Michigan Clinical Research Unit for Blood glucose Clamp studies. Each subject will have a Euglycemic clamp (normal blood sugar clamp) for 4 hours and a hyperglycemic clamp (elevated blood sugar to 300) for 4 hours. Once the subject is clamped, bloods and urine will be collected to assay for specific metabolomics and proteomic biomarkers. We will perform the same clamps for each cohort.

Each cohort group will be admitted to the Michigan Clinical Research Unit for Blood glucose Clamp studies. Each subject will have a Euglycemic clamp (normal blood sugar clamp) for 4 hours and a hyperglycemic clamp (elevated blood sugar to 300) for 4 hours. Once the subject is clamped, bloods and urine will be collected to assay for specific metabolomics and proteomic biomarkers. We will perform the same clamps for each cohort.

Outcomes

Primary Outcome Measures

Difference in the levels of TCA cycle metabolites between groups during euglycemia and hyperglycemia
Investigators will perform 4 hour Euglycemic and 4 hr hyperglycemic glucose clamps on each subject once. The Investigators will have 4 different groups of subjects. At specific time points during the clamps, the investigators will draw blood samples for measurement of metabolic assays and flux . The investigators will also collect spot urine samples for metabolic assay and flux.

Secondary Outcome Measures

Full Information

First Posted
March 19, 2013
Last Updated
June 26, 2018
Sponsor
University of Michigan
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT01823406
Brief Title
Tissue-Specific Metabolic Reprogramming in Diabetic Complications
Acronym
DP3
Official Title
Tissue-Specific Metabolic Reprogramming in Diabetic Complications. Glycemic Clamp Studies to Determine the Real Time Synthesis Rates of Glucose Derived Metabolites in Individuals With Type 1 Diabetes and Healthy Controls.
Study Type
Interventional

2. Study Status

Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
May 2012 (undefined)
Primary Completion Date
August 2017 (Actual)
Study Completion Date
August 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Michigan
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
We will perform blood sugar studies to assess changes in metabolic (biochemical processes that occur within us) profiles associated with high blood sugar and diabetes.
Detailed Description
Objective: To assess steady state and dynamic metabolite changes in subjects with type 1 diabetes with and without microvascular complications and to understand intrinsic differences from non-diabetics in metabolite levels and flux. The hypothesis is that diabetic complications arise from tissue-specific metabolic reprogramming resulting in alterations in fuel utilization which lead to dysfunction of the tissue. To test this hypothesis, we will use sensitive and specific mass spectrometer based metabolomic analysis to measure steady state metabolite levels in plasma and urine from controls subjects and subjects with T1DM, without and with diabetic complications during euglycemic and hyperglycemic clamp studies.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes Mellitus

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
35 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Type 1 Diabetes no complications.
Arm Type
Experimental
Arm Description
Each cohort group will be admitted to the Michigan Clinical Research Unit for Blood glucose Clamp studies. Each subject will have a Euglycemic clamp (normal blood sugar clamp) for 4 hours and a hyperglycemic clamp (elevated blood sugar to 300) for 4 hours. Once the subject is clamped, bloods and urine will be collected to assay for specific metabolomics and proteomic biomarkers. We will perform the same clamps for each cohort.
Arm Title
Type 1 Diabetes with microalbuminuria
Arm Type
Experimental
Arm Description
Each cohort group will be admitted to the Michigan Clinical Research Unit for Blood glucose Clamp studies. Each subject will have a Euglycemic clamp (normal blood sugar clamp) for 4 hours and a hyperglycemic clamp (elevated blood sugar to 300) for 4 hours. Once the subject is clamped, bloods and urine will be collected to assay for specific metabolomics and proteomic biomarkers. We will perform the same clamps for each cohort.
Arm Title
Type 1 Diabetes with advanced complications.
Arm Type
Experimental
Arm Description
Each cohort group will be admitted to the Michigan Clinical Research Unit for Blood glucose Clamp studies. Each subject will have a Euglycemic clamp (normal blood sugar clamp) for 4 hours and a hyperglycemic clamp (elevated blood sugar to 300) for 4 hours. Once the subject is clamped, bloods and urine will be collected to assay for specific metabolomics and proteomic biomarkers. We will perform the same clamps for each cohort.
Arm Title
Aged and sex matched healthy control volunteers
Arm Type
Experimental
Arm Description
Each cohort group will be admitted to the Michigan Clinical Research Unit for Blood glucose Clamp studies. Each subject will have a Euglycemic clamp (normal blood sugar clamp) for 4 hours and a hyperglycemic clamp (elevated blood sugar to 300) for 4 hours. Once the subject is clamped, bloods and urine will be collected to assay for specific metabolomics and proteomic biomarkers. We will perform the same clamps for each cohort.
Intervention Type
Procedure
Intervention Name(s)
Euglycemic clamp (normal blood sugar clamp) for 4 hours
Intervention Type
Procedure
Intervention Name(s)
hyperglycemic clamp (elevated blood sugar to 300) for 4 hours
Primary Outcome Measure Information:
Title
Difference in the levels of TCA cycle metabolites between groups during euglycemia and hyperglycemia
Description
Investigators will perform 4 hour Euglycemic and 4 hr hyperglycemic glucose clamps on each subject once. The Investigators will have 4 different groups of subjects. At specific time points during the clamps, the investigators will draw blood samples for measurement of metabolic assays and flux . The investigators will also collect spot urine samples for metabolic assay and flux.
Time Frame
One time study visit /subject for an average of up to 24 h.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Group 1: T1DM subjects without complications: Group 2: T1DM subjects with microalbuminuria . Group 3: T1DM subjects with advanced diabetes complications Group 4: Age-and-sex-matched healthy control subjects . Inclusion Criteria: General entry criteria: Must have type 1 diabetes > 5 years duration. 18 years of age or older Subjects in the microalbuminuria group will have a history of urinary microalbumin to creatinine ration between 30-300 m/g confirmed on repeat testing while the non-albuminuric group will have a value of less than 30 mg/g. Subjects in advanced complications group will have confirmed Retinopathy, Peripheral and/or Autonomic Neuropathy and nephropathy. Non diabetic individuals will be matched for age and gender and will have normal glucose tolerance, normal lipid metabolism, and normal blood pressure. Exclusion Criteria: Age less than 18 . Women of child-bearing potential who may be pregnant or lactating History of pancreas, kidney or liver transplant History of drug or alcohol use. History of cancer other than basal cell carcinoma or squamous cell skin cancer. Presence of a condition that in the opinion of the investigator would make it unlikely for the subject to complete the study. -
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rodica Pop-Busui, MD,PhD.
Organizational Affiliation
University of Michigan
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States

12. IPD Sharing Statement

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Tissue-Specific Metabolic Reprogramming in Diabetic Complications

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