Trial record 2 of 3739 for:    effects of systemic NO

Adverse Effects of Systemic Hypoglycemia Exposure on Endothelial Function in Humans

This study has been terminated.
(Insufficient Funding)
Sponsor:
Information provided by (Responsible Party):
Medical College of Wisconsin
ClinicalTrials.gov Identifier:
NCT01660009
First received: August 6, 2012
Last updated: April 8, 2015
Last verified: April 2015
  Purpose
Prior work suggests exposure to low glucose levels (hypoglycemia) is associated with increased cardiovascular risk. However, whether there is a causal relationship between cardiovascular events and hypoglycemia remains unclear with conflicting data in the literature. In this study, we plan to study whether acute exposure of patients to clinically relevant (50-60 milligrams/deciliter) levels of hypoglycemia induces or worsens blood vessel endothelial dysfunction- a key 1st step in the development of heart attacks and strokes. This will be determined in humans both with and with type 2 diabetes.

Condition Intervention
Type 2 Diabetes
Other: Glycemic clamping

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: Adverse Effects of Systemic Hypoglycemia Exposure on Endothelial Function in Humans

Resource links provided by NLM:


Further study details as provided by Medical College of Wisconsin:

Primary Outcome Measures:
  • Flow induced Dilation of the Brachial Artery (FMD%) [ Time Frame: 1 hour ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Measurement of total and phosphorylated endothelium-derived NO synthase expression in radial artery endothelial cells. [ Time Frame: 1 hour ] [ Designated as safety issue: No ]
  • Measurement of mitochondrial membrane potential [ Time Frame: 1 hour ] [ Designated as safety issue: No ]
    Performed on captured radial artery endothelial cells.

  • Mitochondrial superoxide production [ Time Frame: 1 hour ] [ Designated as safety issue: No ]
    From capture radial artery endothelial cells.


Enrollment: 5
Study Start Date: June 2012
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hypoglycemia First
Individuals will undergo a hyperinsulinemic hypoglycemic clamp in their 1st study visit after passing screening, and a euglycemic clamp in their second visit.
Other: Glycemic clamping
During hypoglycemic clamping, individuals will have a blood glucose level of 50-60 mg/dL for approximately 1 hour prior to outcome measurements. During euglycemic clamping, individuals will have a blood glucose level of 85-99 mg/dL for approximately 1 hour prior to outcome measurements.
Experimental: Euglycemia First
Individuals will undergo a hyperinsulinemic euglycemic clamp in their 1st study visit after passing screening, and a euglycemic clamp in their second visit.
Other: Glycemic clamping
During hypoglycemic clamping, individuals will have a blood glucose level of 50-60 mg/dL for approximately 1 hour prior to outcome measurements. During euglycemic clamping, individuals will have a blood glucose level of 85-99 mg/dL for approximately 1 hour prior to outcome measurements.

  Eligibility

Ages Eligible for Study:   21 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

- Type 2 Diabetes Inclusion Criteria

  1. Adult age 21 or older
  2. If on 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase reductase therapy, must be on a stable dose for at least 6 weeks prior to enrollment
  3. Diagnosis of type 2 diabetes by a physician as defined by the American Diabetes Association standard criteria: 1) Fasting Plasma glucose at or above 126 mg/dL 2) a two-hour value in an oral glucose tolerance test at or above 200 mg/dL, or 3) a random plasma glucose concentration 200 mg/dL in the presence of symptoms, or 4) glycosylated hemoglobin greater than or equal to 6.5%.

Score of < 4 using the Gold method for assessing hypoglycemia awareness

Inclusion Criteria for Healthy subjects

  1. Adult age 21 or older
  2. No evidence of metabolic syndrome or diabetes, hypertension (BP≥140/90), or high cholesterol (LDL≥160) at the time of screen.

Exclusion Criteria:

  1. History of stroke, peripheral arterial disease, or coronary artery disease (as defined by the presence of at least one coronary stenosis ≥ 40% on angiography or by confirmed history of myocardial infarction by standard criteria)
  2. Evidence of other evident major illness including chronic renal insufficiency(plasma creatinine > 1.4 for women or 1.5 for men), liver disease (aspartate aminotransferase or alanine aminotransferase greater than 2.5 x normal), and cancer currently undergoing therapy or had therapy for cancer within 1 year of enrollment.
  3. Pregnancy as determine by urinary pregnancy test
  4. Subjects on warfarin, oral anti-thrombin inhibitors, or thienopyridines
  5. Subjects who have had changes to dosing of thiazolidinedione, dipeptidyl peptidase-4 (DPP-4) inhibitor, or metformin therapy within 6 weeks of enrollment.
  6. Failed Allen's test in both arms - unable to safely place an arterial line
  7. Glucose reading of < 50 mg/dL and/or episodes of symptomatic hypoglycemia requiring the assistance of another person for recovery in the 2 years prior to enrollment.
  8. History of hypoglycemic convulsions
  9. Current fluoxetine therapy (known to interfere with neuroendocrine response to hypoglycemia)
  10. Glycosylated hemoglobin over 8.5%
  11. On aldosterone antagonist therapy at the time of enrollment
  12. On insulin therapy at the time of screening.
  13. History of allergy to local anesthetic injection like lidocaine.
  14. Age below 21.

Exclusion Criteria for Healthy Subjects:

  1. Meet any of the exclusion criteria for diabetic or metabolic syndrome group Meet criteria for type 2 diabetes or metabolic syndrome
  2. On medication for cholesterol or blood pressure.
  3. History of allergy to local anesthetic injection like lidocaine.
  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: NCT01660009

Locations
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Medical College of Wisconsin
Investigators
Principal Investigator: Michael E Widlansky, MD, MPH Medical College of Wisconsin
  More Information

Responsible Party: Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT01660009     History of Changes
Other Study ID Numbers: MCW-MEW3 
Study First Received: August 6, 2012
Last Updated: April 8, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Medical College of Wisconsin:
Endothelial Function
Hypoglycemia
Mitochondria

Additional relevant MeSH terms:
Hypoglycemia
Glucose Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on July 26, 2016