Rosiglitazone to Reverse Metabolic Defects in Diabetes

NCT00094796 | Completed Phase 2

• 2 other identifiers: 05000905-H-0009
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 2

Brief Summary

This study will examine whether the anti-diabetes medicine rosiglitazone can safely and effectively reverse the early problems of type 2 diabetes and delay the onset of disease in people with pre-diabetes. The underlying problem in people with diabetes or pre-diabetes is insulin resistance (lowered sensitivity to insulin) resulting in poor glucose (sugar) regulation. Rosiglitazone improves the body's sensitivity to insulin. Patients 21 years of age and older who have type 2 diabetes or who are pre-diabetic (glucose intolerant/insulin resistant) may be eligible for this study. Candidates are screened with a medical history, physical examination, blood tests, echocardiography (heart ultrasound), exercise test, brachial artery reactivity test (see below), and possibly a muscle biopsy. Participants take one rosiglitazone tablet daily by mouth for 2 weeks. The dose is then increased to two tablets daily for another 2 weeks and then to 4 tablets daily for the remainder of the 12-week treatment period. In addition to treatment, patients undergo the following tests and procedures:

• Resting and exercise metabolic testing: The amount of oxygen taken in and carbon dioxide exhaled during breathing is measured while the patient rests in a chair and then while he or she exercises on a stationary bicycle or treadmill. Both at rest and during exercise, the patient wears a facemask that measures the amount of oxygen used. During exercise, heart rate is monitored with electrodes on the chest, arms, and thighs. The exercise test is repeated three times, once to become familiar with the test, again the next day to measure exercise capacity, and again 3 days later. The third test is less strenuous and is optional.
• Muscle biopsy (optional): A small area of skin over a calf muscle is numbed with a local anesthetic and a 1-inch incision is made over the muscle. A small amount of muscle tissue is taken and the incision is closed with stitches.
• Brachial reactivity study: This ultrasound study tests how well the patient's arteries widen. The subject rests on a bed for 30 minutes. An ultrasound measuring device is placed over the artery just above the elbow. The size of the artery and blood flow through it are measured before and after inflating a pressure cuff around the forearm. The pressure cuff stops the flow of blood to the arm for a few minutes. After a 15-minute rest, a nitroglycerin tablet (medicine that causes blood vessels to relax) is placed under the patient's tongue. Before and 3 minutes after the nitroglycerin is given, the size of the artery and blood flow through it are measured again.
• Blood samples: Blood samples are collected at the beginning and end of the study and at study visits in between.
• Study visits: Patients come to the Clinical Center biweekly or monthly for a follow-up history, physical examination, and blood tests. At the end of the3-month treatment period, they receive recommendations about possible treatment modifications to best maintain glucose tolerance. Their physicians are informed of how their blood sugar was controlled. Six months after completing the study, patients undergo a final study evaluation and blood tests, and are then invited to return for yearly checkups after that.

Conditions

Diabetes Mellitus, Type II; Insulin Resistance

Keywords

Insulin Resistance; Brachial Artery Reactivity; Endothelial Progenitor Cells; Metabolic Stress Test; Mitochondrial Function; Type 2 Diabetes; T2DM; Pre-Diabetes

Outcome Measures

Primary Outcomes (1)

• Peak VO(2) after 3 months of rosiglitazone therapy compared with baseline VO(2) max.

Interventions

Exercise cardiopulmonary metabolic testing PROCEDURE

Skeletal muscle biopsy PROCEDURE

Brachial artery reactivity testing PROCEDURE

Eligibility Criteria

• Age: 22 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults older than 21 years.
• Subjects must either have:
• Insulin resistance as defined by a fasting blood sugar of greater than 110mg/dl and less than 126 mg/dl and confirmed with the QUICKI test.
• or the diagnosis of T2DM with a HBA1c less than 9%, a fasting insulin level of greater than 6 UIU/ml and a fasting blood glucose level of greater than 125 mg/dl if not on anti-diabetic therapy.
• Subject understands protocol and provides written, informed consent
• Patients must demonstrate the capacity for a near maximal to maximal effort on a treadmill as measured by exercise ventilatory threshold. This will be measured by achieving a peak respiratory exchange ratio greater than or equal to 1.00 during the initial and final peak VO2 exercise tests.

You may not qualify if:

• Significant structural heart disease (e.g. hypertrophic or dilated cardiomyopathy, valvular heart disease) as determined by echocardiography or unstable coronary disease within the last 3 months.
• Uncontrolled hypertension.
• History of Heart Failure.
• Left ventricular ejection fraction less than 55% as measured by screening echocardiogram.
• Subject physically unable to perform treadmill exercise due to neurologic or orthopedic conditions.
• Insulin-dependent diabetes mellitus or current use of thiazolidinediones
• History of adverse events on thiazolidinedione therapy
• Women of childbearing age unless recent pregnancy test is negative.
• Lactating women.
• Serum creatinine greater than 2.5 mg/dl
• Liver transaminase levels greater than 2.5 x upper limit of normal
• History of cancer in the last 5 years
• History of treatment for any illness with stem cell transplantation
• Active inflammatory disease
• Enrollment in a any drug studies within the last 30 days

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (2)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Medical College of Virginia

Richmond, Virginia, United States

Location

Related Publications (3)

• King H, Aubert RE, Herman WH. Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care. 1998 Sep;21(9):1414-31. doi: 10.2337/diacare.21.9.1414.

  PMID: 9727886 BACKGROUND

• Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M; Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001 May 3;344(18):1343-50. doi: 10.1056/NEJM200105033441801.

  PMID: 11333990 BACKGROUND

• Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002 Feb 7;346(6):393-403. doi: 10.1056/NEJMoa012512.

  PMID: 11832527 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Insulin Resistance; Glucose Intolerance

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism; Hyperglycemia

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: October 22, 2004
• First Posted: October 25, 2004
• Study Start: October 20, 2004
• Study Completion: September 3, 2008
• Last Updated: July 2, 2017

Record last verified: 2008-09-03

Locations

US (2)