The Effect of Losartan in Bicuspid Aortic Valve Patients

• Sponsor: University of Michigan (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01390181
• Collaborator: (none)
• Enrollment: 4
• Location: 1
• Arm: 1
• Duration (Months): 28
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Bicuspid Aortic Valve; Thoracic Aortic Aneurysm	Drug: Cozaar	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Effect of Losartan Treatment on Matrix Metalloproteinase Levels and Outcomes in Bicuspid Aortic Valve Patients
• Study Start Date: Sep 1, 2011
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Losartan	Drug: Cozaar; Angiotensin II Receptor Blocker; Other Names: Losartan

Outcome Measures

Primary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan	Ann Arbor	Michigan	United States	48109

Sponsors and Collaborators

• University of Michigan

Investigators

• Principal Investigator: Anna Booher, MD, University of Michigan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Anna Booher, MD, University of Michigan
• ClinicalTrials.gov Identifier: NCT01390181
• Other Study ID Numbers: HUM00048364
• First Posted: Jul 8, 2011
• Last Update Posted: Apr 14, 2017
• Last Verified: Mar 1, 2017

• Additional relevant MeSH terms: Aneurysm; Aortic Aneurysm; Bicuspid Aortic Valve Disease; Aortic Aneurysm, Thoracic; Heart Valve Diseases; Losartan

Study Results

Participant Flow

Arm/Group Title	Losartan
Arm/Group Description	Cozaar: Angiotensin II Receptor Blocker
Period Title: Overall Study
STARTED	4
COMPLETED	0
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Losartan
Arm/Group Description	Cozaar: Angiotensin II Receptor Blocker
Overall Participants	4
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	4 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	2 50%
Male	2 50%
Region of Enrollment (participants) [Number]
United States	4 100%

Outcome Measures

1. Primary Outcome

Title	Inflammatory Markers Levels
Description	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

Outcome Measure Data

Analysis Population Description

No participants were analyzed because the study terminated prior to data collection for final primary outcome measure.

Arm/Group Title	Losartan
Arm/Group Description	Cozaar: Angiotensin II Receptor Blocker
Measure Participants	0

Adverse Events

Time Frame	6 months (study was terminated prior to proposed completion)
Arm/Group Title	Losartan
Arm/Group Description	Cozaar: Angiotensin II Receptor Blocker
All Cause Mortality
	Losartan
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Losartan
	Affected / at Risk (%)	# Events
Total	0/4 (0%)
Other (Not Including Serious) Adverse Events
	Losartan
	Affected / at Risk (%)	# Events
Total	2/4 (50%)
Cardiac disorders
Increase in Blood Pressure	1/4 (25%)	1
Cardiace Disorder	1/4 (25%)	1
General disorders
Fatigue	1/4 (25%)	1
Musculoskeletal and connective tissue disorders
Fall	1/4 (25%)	1
Nervous system disorders
Shingles	1/4 (25%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.