Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This study will test the hypothesis that reduction in release of free fatty acids from adipocytes will restore insulin-mediated endothelium-dependent vasodilation and skeletal muscle glucose metabolism in subject with type 2 diabetes.
During the past two decades, there has been a steady increase in the incidence of diabetes mellitus, such that nearly 17 million people are now afflicted. The vast majority of these have type 2 diabetes. Over the next 40 years, the type 2 diabetic population in the United States is expected to increase to nearly 30 million.
Diabetes substantially increases the risk of atherosclerosis, and thereby, cardiovascular morbidity and mortality. Indeed, cardiovascular disease causes more than 50% of the mortality in patients with diabetes. People with type 2 diabetes manifest two cardinal signs of dysmetabolism: hyperglycemia and insulin resistance. Insulin resistance is a progressive phenomenon that occurs well before the onset of frank diabetes, and results in alterations in insulin signaling. Experimental studies suggest that insulin signaling is required for vascular homeostasis, and its impairment is associated with endothelial dysfunction. In the clinical setting, insulin resistance is associated with atherosclerosis and predicts cardiovascular events independent of hyperglycemia. Therefore, we will study the importance of insulin signaling in endothelial biology in humans and the effects of free fatty acids on endothelial function in people with type 2 diabetes.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Active Comparator | Acipimox treatment for 7 days |
|
| 2 | Placebo Comparator | placebo treatment for 7 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| acipimox | Drug | subjects will receive acipimox 250 mg orally every 6 hours (or matching placebo) for 7 days, including a dose at 6am on the morning of the study testing visit |
|
| Measure | Description | Time Frame |
|---|---|---|
| Flow-mediated Dilation After Placebo or Acipimox Treatment Between Healthy Controls and Those With Metabolic Syndrome | Flow mediated dilation is calculated as follows: A resting arterial diameter measurement is obtained using the average of 10 EKG-gated ultrasound images. Next, an occlusive pressure is applied (using a blood pressure cuff inflated to a suprasystolic pressure)for a period of 5 minutes. After 5 minutes, the cuff is rapidly deflated. This produces a reactive hyperemic response which is captured via ultrasound at 1 minute post cuff deflation (also 10 EKG-gated images averaged). The diameter of the artery following reactive hyperemia is calculated and compared to the resting diameter to obtain a percent dilation. This is flow-mediated dilation. | 7 days |
| Difference in Insulin-mediated Skeletal Muscle Glucose Utilization Between Test Agent and Placebo | Insulin sensitivity (M) is measured by using a hyperinsulinaemic-euglycaemic clamp. Insulin sensitivity (M) was calculated as the average glucose infusion rate (mg/kg of body weight per min) over the last 30 min of the clamp. Higher values indicate better outcomes (more insulin sensitive), while lower values indicate more insulin resistance. | baseline, 7 days |
Not provided
Not provided
Inclusion Criteria:
Exclusion Criteria:
Type 2 Diabetics
(Note: subjects taking angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) must stop these medications for 2 weeks prior to taking study drug. If blood pressure rises to >140/90, subjects will be prescribed an alternative medication or be withdrawn from the study.
Healthy Volunteers
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Mark Creager, M.D. | Brigham and Women's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brigham & Women's Hospital | Boston | Massachusetts | 02115 | United States |
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Healthy Controls, Placebo First, Then Acipimox | The study is a randomized, placebo-controlled, double-blind, cross-over trial in subjects with the metabolic syndrome and healthy subjects with interventions assessed over one day of treatment and a washout period of 4 weeks. Acipimox (Pharmacia and Upjohn (Pfizer), Kalamazoo, MI), 250 mg, or matching placebo will be given at 7 PM, 1 AM, and 7 AM, and 11 AM prior to and on the day of study. |
| FG001 | Healthy Controls, Acipimox First, Then Placebo | The study is a randomized, placebo-controlled, double-blind, cross-over trial in subjects with the metabolic syndrome and healthy subjects with interventions assessed over one day of treatment and a washout period of 4 weeks. Acipimox (Pharmacia and Upjohn (Pfizer), Kalamazoo, MI), 250 mg, or matching placebo will be given at 7 PM, 1 AM, and 7 AM, and 11 AM prior to and on the day of study. |
| FG002 | Metabolic Syndrome, Placebo First, Then Acipimox | The study is a randomized, placebo-controlled, double-blind, cross-over trial in subjects with the metabolic syndrome and healthy subjects with interventions assessed over one day of treatment and a washout period of 4 weeks. Acipimox (Pharmacia and Upjohn (Pfizer), Kalamazoo, MI), 250 mg, or matching placebo will be given at 7 PM, 1 AM, and 7 AM, and 11 AM prior to and on the day of study. |
| FG003 | Metabolic Syndrome, Acipimox First, Then Placebo | The study is a randomized, placebo-controlled, double-blind, cross-over trial in subjects with the metabolic syndrome and healthy subjects with interventions assessed over one day of treatment and a washout period of 4 weeks. Acipimox (Pharmacia and Upjohn (Pfizer), Kalamazoo, MI), 250 mg, or matching placebo will be given at 7 PM, 1 AM, and 7 AM, and 11 AM prior to and on the day of study. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Study Visit Day 1 |
| |||||||||||||
| Study Visit Day 2 |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Healthy Controls | |
| BG001 | Metabolic Syndrome | |
| BG002 | Total |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Flow-mediated Dilation After Placebo or Acipimox Treatment Between Healthy Controls and Those With Metabolic Syndrome | Flow mediated dilation is calculated as follows: A resting arterial diameter measurement is obtained using the average of 10 EKG-gated ultrasound images. Next, an occlusive pressure is applied (using a blood pressure cuff inflated to a suprasystolic pressure)for a period of 5 minutes. After 5 minutes, the cuff is rapidly deflated. This produces a reactive hyperemic response which is captured via ultrasound at 1 minute post cuff deflation (also 10 EKG-gated images averaged). The diameter of the artery following reactive hyperemia is calculated and compared to the resting diameter to obtain a percent dilation. This is flow-mediated dilation. | Posted | Mean | Standard Deviation | Flow mediated dilation | 7 days |
|
3 months
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Healthy Controls | Healthy subjects will be ≥18 years of age and have no known medical problems, have a normal cardiovascular exam and a fasting glucose <110 mg/dL determined during a screening visit. |
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mark A. Creager | Brigham and Women's Hospital | 603-650-8283 | Mark.A.Creager@hitchcock.org |
Not provided
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C027696 | acipimox |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| placebo | Drug | matching placebo |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
Total of all reporting groups
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Healthy Controls, Acipimox Treatment |
| OG002 | Metabolic Syndrome, Placebo Treatment |
| OG003 | Metabolic Syndrome, Acipimox Treatment |
|
|
| Primary | Difference in Insulin-mediated Skeletal Muscle Glucose Utilization Between Test Agent and Placebo | Insulin sensitivity (M) is measured by using a hyperinsulinaemic-euglycaemic clamp. Insulin sensitivity (M) was calculated as the average glucose infusion rate (mg/kg of body weight per min) over the last 30 min of the clamp. Higher values indicate better outcomes (more insulin sensitive), while lower values indicate more insulin resistance. | The data for this outcome measure was lost when the investigator left the institution, so the measure was not analyzed. | Posted | baseline, 7 days |
|
|
| 0 |
| 18 |
| 0 |
| 18 |
| 0 |
| 18 |
| EG001 | Metabolic Syndrome | The patient population for this specific aim will include non-diabetic subjects with the metabolic syndrome who are ≥18 years of age. The metabolic syndrome will be defined as the presence of 4 or 5 components of the syndrome as defined by the National Cholesterol Education Program including abdominal obesity, elevated fasting blood sugar (110 mg/dL< glucose < 126 mg/dL) (54), low HDL, elevated fasting blood triglycerides (Trigs > 150 mg/dL), and hypertension (BP > 140/90 mm HG) (55). Patients will be excluded from this protocol if they have any of the following: diabetes mellitus, untreated hypercholesterolemia (LDL > 75th percentile for age), cigarette smoking within 1 year, renal insufficiency (creatinine > 1.4 mg/dl), blood dyscrasia, or hepatic dysfunction (ALT > 2x normal). Potential subjects will also be excluded if they are infected with the human immunodeficiency virus or have psychiatric illness requiring more than one medication for depression or anxiety. | 0 | 22 | 0 | 22 | 0 | 22 |
Not provided
Not provided
| D004700 | Endocrine System Diseases |
| D006946 | Hyperinsulinism |