Effect of Insulin Sensitizer Therapy on Atherothrombotic and Inflammatory Profiles Associated With Insulin Resistance
연구 개요
상세 설명
Individuals with diabetes mellitus (DM) are disproportionately affected by atherothrombotic disorders, including cardiovascular, cerebrovascular, and peripheral vascular diseases. Atherothrombotic disease risk and mortality are also increased with metabolic syndrome, a constellation of risk factors present in more than 34% of adults, even in absence of diabetes. Yet, large clinical trials of diabetes therapies have shown that conventional cardiovascular disease (CVD) risk factors, specifically hyperglycemia and hypertension, do not fully account for increased CVD risk associated with DM.
There may be an etiologic link among insulin resistance, inflammation and thrombotic events. This study seeks to determine if certain two diabetes medications (the insulin sensitizing medications) will affect certain biomarkers (or laboratory tests) for CVD in individuals with untreated DM or impaired fasting glucose.
Patients will be screened for inclusion into this this double-blinded, randomized), placebo-controlled study. If inclusion criteria are met and exclusion criteria not met, patients will be enrolled in the the study. Half of the subjects will be randomized (like the flip of a coin) to take two insulin sensitizing, anti-diabetic drugs pioglitazone (Actos) and metformin (Glucophage) taken together for three months and the other half of the subjects will take corresponding placebo (dummy) tablets.
Laboratory measurements will be obtained on the morning(s) following the two in-patient overnight stays in the Mayo Clinic Clinical Research Unit. The first stay will be at baseline and the second stay will be 3 months after baseline. Insulin sensitivity will be measured in the morning following a standardized meal the preceding night, and after an overnight fast.
The changes (from baseline to 3 months) in insulin sensitivity, glycemic control, the lipid profile, thrombotic markers and inflammatory markers will be determined and compared between the two arms of the study (placebo versus insulin sensitizing drugs).
연구 유형
등록 (실제)
단계
- 2 단계
연락처 및 위치
연구 장소
-
-
Minnesota
-
Rochester, Minnesota, 미국, 55905
- Mayo Clinic
-
-
참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion criteria:
- We will study 30 patients with Type 2 Diabetes or impaired fasting glucose (15 men & 15 women) who are > 20 years old.
- Only patients who use lifestyle modification to manage their diabetes and are not on any oral hypoglycemic agents or insulin will be included.
- We will enroll subjects who have fasting glucose concentration greater than 100 mg/dl on two consecutive occasions and have a Body Mass Index between 27-36 kg/m^2.
Exclusion Criteria:
- We will exclude patients whose blood glucose is above 180 mg/dl. This will avoid the need to perform home glucose monitoring and the potential of unblinding the study by the volunteers.
- Patients taking oral hypoglycemic agents or insulin would be excluded.
- Any diseases such as active cardiovascular disease, liver diseases, kidney failure (males with serum creatinine >= 1.5mg/dl, females >=1.4 mg/dl), active endocrinopathies, debilitating chronic disease, anemia, symptoms of undiagnosed illness, history of alcoholism (alcohol use > 4oz/day) or substance abuse, chronic neurological diseases including Alzheimer's disease, stroke, etc, myopathies or any other active disease that may potentially affect the outcome measures.
- Patients on medicines such as beta blockers, corticosteroids, tricyclics, benzodiazepines, opiates, barbiturates, anticoagulants and any other drugs or preparations that may affect mitochondrial function will be excluded.
- People allergic to any of the class of drug such as lidocaine will also be excluded.
- People with pacemakers, certain aneurysm clips and claustrophobia will also be excluded as they cannot undergo magnetic resonance imaging.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 더블
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
활성 비교기: Insulin Sensitizer Therapy
Two insulin sensitizing drugs will be taken together for 3 months; metformin 1000 mg twice daily plus pioglitazone 45 mg daily.
|
To minimize side effects the metformin will be initiated at 500 mg twice daily with meals and increased to 1 gm twice daily with meals after two weeks and continue to a total of 3 months of dosing.
다른 이름들:
To minimize side effects, the pioglitazone will be initiated at 30 mg daily and increased to 45 mg daily after two weeks, and continue to a total of 3 months of dosing.
다른 이름들:
|
|
위약 비교기: Placebo
Placebo tablets were used to match the active comparator drugs and dosing regimen.
|
Placebo tablets matching the metformin and pioglitazone tablets are given in the same regimen as the active drug arm for 3 months.
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Change From Baseline in Insulin Sensitivity as Measured by Glucose Infusion Rate (GIR)
기간: Baseline, 3 months
|
Insulin sensitivity was measured the morning after an overnight fast during an in-patient stay in the Clinical Research Unit & was determined by the mean GIR necessary to maintain euglycemia during a hyperinsulinemic (1.5 mcIU/kg of FFM per minute)-euglycemic (85-95 mg/dL) clamp.
The clamp is an 8 hour process where a hand vein is catheterized to collect blood samples and intravenous lines are used to infuse glucose, saline, insulin, phenylalanine and amino acid solutions at at pre-specified times/rates.
The mean GIR was calculated as the rate per kilograms of fat-free mass (FFM) during 4 hours of steady-state (hours 4-8 of the 8 hour clamp) reported as micromols/kilogram of FFM per minute.
The FFM was measured by dual-energy x-ray absorptiometry (DEXA) scan.
Insulin was infused with 5% essential amino acid solution (3mL/kg of FFM/hour) to prevent the insulin-dependent decrease of amino acids during insulin infusion.
|
Baseline, 3 months
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Change From Baseline in Fasting Blood Glucose Level
기간: Baseline, 3 months
|
Glucose (sugar) was measured in the blood and reported in milligrams per deciliter (mg/dL).
|
Baseline, 3 months
|
|
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
기간: Baseline, 3 months
|
HbA1c is a measure of average blood sugar levels over the preceding 3 month period.
HbA1c was measured by ion-exchange chromatography and reported as a percentage.
|
Baseline, 3 months
|
|
Change From Baseline in Insulin Levels
기간: Baseline, 3 months
|
Insulin levels in the blood were measured by immunoenzymatic assay and reported in micro International Units per milliliter (mcIU/mL).
|
Baseline, 3 months
|
|
Change From Baseline in Lipid Profile
기간: Baseline, 3 months
|
Change in lipids were measured by the change from baseline to 3 months of triglycerides, high-density lipoprotein cholesterol (HDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C).
All were reported in milligrams/deciliter (mg/dL).
|
Baseline, 3 months
|
|
Change From Baseline in the Thrombotic Biomarker Fibrinogen
기간: Baseline, 3 months
|
Fibrinogen was measured by thrombin clotting rate assay (Beckman Coulter, Inc. Brea, California) and reported in milligrams/deciliter (mg/dL).
|
Baseline, 3 months
|
|
Change From Baseline in the Thrombotic Biomarker Plasminogen Activator Inhibitor-1 (PAI-1)
기간: Baseline, 3 months
|
PAI-1 was measured by enzyme-linked immunosorbent assay (Diagnostica Stago Inc., Parsippany, New Jersey) and reported in nanograms per milliliter (ng/mL).
|
Baseline, 3 months
|
|
Change From Baseline in the Inflammatory Biomarker Interleukin 6 (IL-6)
기간: Baseline, 3 months
|
IL-6 is an inflammatory cytokine and reported in picograms per deciliter (pg/dL).
|
Baseline, 3 months
|
|
Change From Baseline in the Inflammatory Biomarker C-Reactive Protein (CRP)
기간: Baseline, 3 months
|
CRP is an inflammatory cytokine and is reported in milligrams per deciliter (mg/dL).
|
Baseline, 3 months
|
|
Change From Baseline in Inflammatory Biomarker Tumor Necrosis Factor-alpha (TNF-α)
기간: Baseline, 3 month
|
TNF-α is an inflammatory cytokine and is reported in picograms/milliliter (pg/mL).
|
Baseline, 3 month
|
|
Change From Baseline in the Inflammatory Biomarker Adiponectin
기간: Baseline, 3 months
|
Adiponectin is an anti-inflammatory cytokine and is reported in milligrams per milliliter (mg/mL).
|
Baseline, 3 months
|
기타 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Change From Baseline in Body Mass Index
기간: Baseline, 3 months
|
Body Mass Index (BMI) is a health index for comparing weight to height.
BMI is a person's weight in kilograms (kg) divided by his or her height in meters squared.
The body mass index is an indication if a person is at a suitable weight for his height on an approximation of body fat.
|
Baseline, 3 months
|
|
Change From Baseline in Body Fat
기간: Baseline, 3 months
|
Body fat is reported as a percentage of body weight.
|
Baseline, 3 months
|
|
Change From Baseline in Fat-Free Mass (FFM)
기간: Baseline, 3 months
|
FFM was measured using dual energy x-ray absorptiometry (DEXA) scans and is reported in kilograms (kg).
|
Baseline, 3 months
|
공동 작업자 및 조사자
간행물 및 유용한 링크
일반 간행물
- McCoy RG, Irving BA, Soop M, Srinivasan M, Tatpati L, Chow L, Weymiller AJ, Carter RE, Nair KS. Effect of insulin sensitizer therapy on atherothrombotic and inflammatory profiles associated with insulin resistance. Mayo Clin Proc. 2012 Jun;87(6):561-70. doi: 10.1016/j.mayocp.2012.02.014. Erratum In: Mayo Clin Proc. 2013 Aug;88(8):903-4.
- Irving BA, Carter RE, Soop M, Weymiller A, Syed H, Karakelides H, Bhagra S, Short KR, Tatpati L, Barazzoni R, Nair KS. Effect of insulin sensitizer therapy on amino acids and their metabolites. Metabolism. 2015 Jun;64(6):720-8. doi: 10.1016/j.metabol.2015.01.008. Epub 2015 Jan 22.
유용한 링크
연구 기록 날짜
연구 주요 날짜
연구 시작
기본 완료 (실제)
연구 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정)
연구 기록 업데이트
마지막 업데이트 게시됨 (추정)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .