Back to resultsSignaling Mechanisms and Vascular Function in Patients With Diabetes Mellitus
Primary Purpose
Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ebselen
Placebo
Sponsored by
About this trial
This is an interventional basic science trial for Type 1 Diabetes Mellitus
Eligibility Criteria
Inclusion Criteria:
- Subjects with diabetes mellitus will be eligible if they are receiving dietary treatment for hyperglycemia, sulfonylureas, metformin or insulin
Exclusion Criteria:
- Any diabetic subject with a HgbA1C level of <7% or >11%
- Evidence of atherosclerosis
- symptoms of angina
- symptoms of claudication
- symptoms of cerebrovascular ischemia
- findings of arterial occlusive disease, as would be suggested by decreased pulses, asymmetric blood pressure, bruits or reduced limb pressure measurements
- hypertension defined as a systolic blood pressure > = 150 mmHg and a diastolic blood pressure >= 95 mmHg; (allowable blood pressure medications for diabetic subjects include calcium channel blockers, alpha and beta adrenergic blockers, and diuretics)
- hypercholesterolemia, defined as total cholesterol levels greater than 75th percentile for age and sex and LDL cholesterol levels >130mg/dL.
- renal insufficiency (serum creatinine >1.5 mg/dL for men; >1.2 mg/dL for women)
- hepatic dysfunction defined as liver enzyme abnormalities > two times the upper limit of normal
- chronic pulmonary disease
- congestive heart failure
- pregnancy (or subjects planning to become pregnant);
- history of cigarette smoking within the last five years;
history of clinically significant coronary artery or cerebrovascular disease (defined as MI or stroke within 6 months, or presence of unstable angina)
- use of any, vasoactive, cardioactive, or non-steroidal anti-inflammatory medications within 24 hours of vascular testing visits
Sites / Locations
- Brigham and Women's Hosptial
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Active Comparator
Arm Label
2
1
Arm Description
Placebo
Ebselen
Outcomes
Primary Outcome Measures
Endothelium-dependent and endothelium-independent vasodilation of peripheral resistance and conduit vessels will be studied in diabetic (type 1 and 2) and healthy subjects two weeks following randomization to the ebselen or placebo.
Secondary Outcome Measures
Full Information
NCT ID
NCT00762671
First Posted
September 26, 2008
Last Updated
September 29, 2008
Sponsor
Brigham and Women's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT00762671
Brief Title
Signaling Mechanisms and Vascular Function in Patients With Diabetes Mellitus
Official Title
Signaling Mechanisms and Vascular Function in Patients With Diabetes Mellitus
Study Type
Interventional
2. Study Status
Record Verification Date
September 2008
Overall Recruitment Status
Completed
Study Start Date
May 1999 (undefined)
Primary Completion Date
October 2007 (Actual)
Study Completion Date
October 2007 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Brigham and Women's Hospital
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of the study is to learn how blood vessel function is altered by diabetes. We are studying an investigational drug, Ebselen, to see if it can improve the ability of blood vessels to relax (widen).
Detailed Description
A major cause of death and disability in patients with diabetes mellitus is atherosclerosis. Endothelial dysfunction is an important, if not primary, factor in atherogenesis. Nitric oxide is an important substance made and released by the endothelium. Many prior studies in animals and humans have shown that the ability of the blood vessel to dilate is impaired in diabetes. This process of vasodilation is mediated by a substance, nitric oxide, which is thought to be highly susceptible to destruction by oxidant molecules. In previous studies, we found that acute administration of the antioxidant, vitamin C, improves endothelium-dependent vasodilation in blood vessels of patients with type 1 and type 2 diabetes. This suggests that by scavenging oxidants, such as superoxide, vitamin C may reduce the destruction of nitric oxide and thereby preserve endothelial function. Additional mechanisms, including activation of a substance called protein kinase C, and oxidant stress from excess soluble peroxides may be present in diabetes and interact with oxidant stress to cause endothelial dysfunction in patients with diabetes. Accordingly, we would like to study both of these mechanisms to determine their contribution to endothelial dysfunction.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 2, Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Actual)
8. Arms, Groups, and Interventions
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
Placebo
Arm Title
1
Arm Type
Active Comparator
Arm Description
Ebselen
Intervention Type
Drug
Intervention Name(s)
Ebselen
Intervention Description
150 mg BID for 2 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo 1 po BID for 2 weeks
Primary Outcome Measure Information:
Title
Endothelium-dependent and endothelium-independent vasodilation of peripheral resistance and conduit vessels will be studied in diabetic (type 1 and 2) and healthy subjects two weeks following randomization to the ebselen or placebo.
Time Frame
one testing visit every 4 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Subjects with diabetes mellitus will be eligible if they are receiving dietary treatment for hyperglycemia, sulfonylureas, metformin or insulin
Exclusion Criteria:
Any diabetic subject with a HgbA1C level of <7% or >11%
Evidence of atherosclerosis
symptoms of angina
symptoms of claudication
symptoms of cerebrovascular ischemia
findings of arterial occlusive disease, as would be suggested by decreased pulses, asymmetric blood pressure, bruits or reduced limb pressure measurements
hypertension defined as a systolic blood pressure > = 150 mmHg and a diastolic blood pressure >= 95 mmHg; (allowable blood pressure medications for diabetic subjects include calcium channel blockers, alpha and beta adrenergic blockers, and diuretics)
hypercholesterolemia, defined as total cholesterol levels greater than 75th percentile for age and sex and LDL cholesterol levels >130mg/dL.
renal insufficiency (serum creatinine >1.5 mg/dL for men; >1.2 mg/dL for women)
hepatic dysfunction defined as liver enzyme abnormalities > two times the upper limit of normal
chronic pulmonary disease
congestive heart failure
pregnancy (or subjects planning to become pregnant);
history of cigarette smoking within the last five years;
history of clinically significant coronary artery or cerebrovascular disease (defined as MI or stroke within 6 months, or presence of unstable angina)
use of any, vasoactive, cardioactive, or non-steroidal anti-inflammatory medications within 24 hours of vascular testing visits
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark A Creager, MD
Organizational Affiliation
Brigham and Women's Hosptial
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brigham and Women's Hosptial
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
32483557
Citation
Garland M, Hryckowian AJ, Tholen M, Bender KO, Van Treuren WW, Loscher S, Sonnenburg JL, Bogyo M. The Clinical Drug Ebselen Attenuates Inflammation and Promotes Microbiome Recovery in Mice after Antibiotic Treatment for CDI. Cell Rep Med. 2020 Apr 21;1(1):100005. doi: 10.1016/j.xcrm.2020.100005.
Results Reference
derived
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Signaling Mechanisms and Vascular Function in Patients With Diabetes Mellitus
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