Bicuspid Aortic Valve, Thoracic Aortic Aneurysm
Conditions
Brief summary
The specific aims of this study are to: * Establish baseline levels of circulating MMP-2 and -9 , TIMP-1and- 2 and TGFB levels in individuals with bicuspid aortic valve and ascending aortic or aortic sinus measurements \>40mm. * Assess the effect on MMP levels during treatment with losartan, an angiotensin II receptor blocking agent. * In the setting of losartan therapy for one year, evaluate the response of MMP levels in these patients, and clinical outcomes including effects on aortic growth rate
Interventions
DRUGCozaar
Angiotensin II Receptor Blocker
Sponsors
University of Michigan
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Adults \>age 18 years and \< 65 years old * Able to give informed consent * Presence of a bicuspid aortic valve (functional or true bicommisural)and ascending aorta or sinus of Valsalva \>4.0cm * No contraindications to treatment with Losartan, an Angiotensin II receptor blocker * Able to safely participate in a 4 week drug washout period if currently taking an angiotensin II receptor blocker or ACE inhibitor.
Exclusion criteria
* Unable to safely take losartan due to one or more of the following: * Hypersensitivity to losartan or other angiotensin receptor blockers * Pregnancy * Nursing mothers * History of angioedema * Hypotension - chronically volume depleted patients * Hepatic or renal impairment (Cr\>1.5mg/dL) * Hyperkalemia (K+\>4.8) * Renal artery stenosis * Severe congestive heart failure (class III-IV) * Currently taking potassium supplements or salt substitutes containing potassium * Currently taking lithium * Prior surgical intervention to aorta or aortic valve * Unable or unwilling to give informed consent and follow up with study activities * Currently taking an angiotensin receptor blocker or ACE inhibitor specifically for hypertension and are therefore unable to or are unwilling to participate in a 4 week drug washout period. * Females of child bearing who are unwilling to practice adequate birth control throughout the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Inflammatory Markers Levels | Baseline and 12 months | Changes in levels of Matrix Metalloproteinase (MMP-2, MMP-9), Tissue Inhibitor of Metalloproteinases (TIMP 1, TIMP 2), & Transforming Growth Factor-Beta (TGFB) in circulation while taking medication from baseline at 3 months, 6 months and 12 months. The 12 month levels were the primary outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Losartan Cozaar: Angiotensin II Receptor Blocker | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Study Terminated due to Low Accrual | 3 |
Baseline characteristics
| Characteristic | Losartan |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Region of Enrollment United States | 4 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
Inflammatory Markers Levels
Changes in levels of Matrix Metalloproteinase (MMP-2, MMP-9), Tissue Inhibitor of Metalloproteinases (TIMP 1, TIMP 2), & Transforming Growth Factor-Beta (TGFB) in circulation while taking medication from baseline at 3 months, 6 months and 12 months. The 12 month levels were the primary outcome.
Time frame: Baseline and 12 months
Population: No participants were analyzed because the study terminated prior to data collection for final primary outcome measure.