Tissue-Specific Metabolic Reprogramming in Diabetic Complications (DP3)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by University of Michigan
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Rodica Pop-Busui, University of Michigan
ClinicalTrials.gov Identifier:
NCT01823406
First received: March 19, 2013
Last updated: December 13, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention
Type 1 Diabetes Mellitus
Procedure: Euglycemic clamp (normal blood sugar clamp) for 4 hours
Procedure: hyperglycemic clamp (elevated blood sugar to 300) for 4 hours

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
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.

Resource links provided by NLM:


Further study details as provided by University of Michigan:

Primary Outcome Measures:
  • Difference in the levels of TCA cycle metabolites between groups during euglycemia and hyperglycemia [ Time Frame: One time study visit /subject for an average of up to 24 h. ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 40
Study Start Date: May 2012
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Type 1 Diabetes no complications.
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.
Procedure: Euglycemic clamp (normal blood sugar clamp) for 4 hours Procedure: hyperglycemic clamp (elevated blood sugar to 300) for 4 hours
Experimental: Type 1 Diabetes with microalbuminuria
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.
Procedure: Euglycemic clamp (normal blood sugar clamp) for 4 hours Procedure: hyperglycemic clamp (elevated blood sugar to 300) for 4 hours
Experimental: Type 1 Diabetes with advanced complications.
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.
Procedure: Euglycemic clamp (normal blood sugar clamp) for 4 hours Procedure: hyperglycemic clamp (elevated blood sugar to 300) for 4 hours
Experimental: Aged and sex matched healthy control volunteers
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.
Procedure: Euglycemic clamp (normal blood sugar clamp) for 4 hours Procedure: hyperglycemic clamp (elevated blood sugar to 300) for 4 hours

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.

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  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01823406

Locations
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Cynthia D Plunkett, RN    734-936-8065    cplunket@umich.edu   
Contact: Rodica Pop-Busui, MD, PhD    734-763-3056    rpbusui@umich.edu   
Principal Investigator: Rodica Pop-Busui, MD,PhD.         
Sponsors and Collaborators
University of Michigan
Investigators
Principal Investigator: Rodica Pop-Busui, MD,PhD. University of Michigan
  More Information

No publications provided

Responsible Party: Rodica Pop-Busui, Associate Professor Internal Medicine, MEND Division, University of Michigan
ClinicalTrials.gov Identifier: NCT01823406     History of Changes
Other Study ID Numbers: HUM00060967, 1DP3DK094292-01
Study First Received: March 19, 2013
Last Updated: December 13, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Diabetes Complications
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on September 29, 2014