The Role of Endothelin-1 in Sickle Cell Disease

• Status: Completed
• Trial end date: 2019-11-30
• Target enrollment: 0
• Participant gender: All

Summary

The primary goal of the study is to determine the safety and tolerability of ambrisentan. It is also expected that ambrisentan will improve blood flow in the lungs, decrease inflammation, and reduce pain in sickle cell patients. An additional goal is to evaluate the use of select biomarkers in evaluating sickle nephropathy.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Augusta University
• Collaborators: Gilead Sciences; National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Ambrisentan

Criteria

Inclusion Criteria:

1. SS or Sβo-thalassemia

2. Age 18-65 years

3. Microalbuminuria (24-hour albumin 150-300 mg) or macroalbuminuria (24-hour albumin >300 mq) OR random urine albumin-creatinine ratio (MA Random) ≥ 30 µg/ mg creatinine

4. Subjects can have Stage 1, II, or III chronic kidney disease (CKD)

5. Subjects can be on hydroxyurea, ACE inhibitors (ACEi), or angiotensin receptor blockers (ARBs) for a period of 3 months or greater

6. Females of child bearing potential must agree to use two forms of birth control with one being a barrier method; abstinence is an acceptable form of birth control

Exclusion Criteria:

1. Other genotypes of SCD

2. History of renal transplant

3. Chronic kidney disease (Stage IV and V including patients on hemo dialysis or peritoneal dialysis)

4. Patients on chronic transfusion therapy

5. Uncontrolled/poorly controlled hypertension or history of hypertension pre-dating proteinuria or

6. Known history of HIV, Hepatitis C, and/or diabetes

7. Peripheral edema

8. History of congestive heart failure or pulmonary edema

9. Recent history of coronary artery disease

10. Pregnant or breast feeding

11. Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) >3-fold upper limit of normal

12. Albumin <2.5 gm/dl

13. Hemoglobin < 6 gm/dL

14. History of non-compliance with medications and clinic visits; or Inability to give informed consent; or Patient deemed ineligible or unsuitable in the judgment of investigators