The Role of Endothelin-1 in Sickle Cell Disease
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ClinicalTrials.gov Identifier: NCT02712346 |
Recruitment Status :
Completed
First Posted : March 18, 2016
Last Update Posted : April 2, 2020
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Sickle Cell Anemia | Drug: Ambrisentan Drug: Placebo | Phase 1 |

Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 26 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Triple (Participant, Care Provider, Investigator) |
Primary Purpose: | Treatment |
Official Title: | The Role of Endothelin-1 in Sickle Cell Disease |
Study Start Date : | September 2015 |
Actual Primary Completion Date : | May 30, 2019 |
Actual Study Completion Date : | November 30, 2019 |

Arm | Intervention/treatment |
---|---|
Experimental: Treatment
Ambrisentan 5 mg PO daily
|
Drug: Ambrisentan
Ambrisentan 5 milligrams a day or a placebo (sugar pill) for twelve weeks
Other Name: Letairis |
Placebo Comparator: Placebo
One inactive pill PO daily
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Drug: Placebo
One inactive pill daily for twelve weeks
Other Name: "Sugar Pill" |
- Safety and Tolerability of ambrisentan in patients with sickle cell disease measured by physical exam, vital signs, blood and urine testing, ECG (specified visits), concomitant medication review, adverse events review [ Time Frame: Day 1 (Baseline) through Day 113 ]
- Efficacy of ambrisentan in improving kidney function in patients with sickle cell disease measured by blood [ Time Frame: Day 1 (Baseline), Day 15, Day 29, Day 57, Day 85, and Day 113 ]measured by blood
- Efficacy of ambrisentan in decreasing TRJ velocity [ Time Frame: Day 1 (Baseline) and at the end of the 12 week treatment period ]measured by echocardiogram
- Efficacy of ambrisentan in decreasing inflammation [ Time Frame: Day 1 (Baseline) through Day 113 ]measurement of inflammatory markers in blood
- Efficacy of ambrisentan in improving micro-circulation [ Time Frame: Day 1 (Baseline) and at the end of the 12 week treatment period ]measured by forearm and skin blood flow measurements
- Efficacy of ambrisentan in improving macro-circulation [ Time Frame: Day 1 (Baseline), and at the end of the 12 week treatment period ]measured by Transcranial Doppler (TCD)
- Efficacy of ambrisentan in improving nociception/pain [ Time Frame: Day 1 (Baseline), and at the end of the 12 week treatment period ]performance of quantitative sensory testing
- Efficacy of ambrisentan in improving kidney function in patients with sickle cell disease measured by urine testing for microalbuminuria/proteinuria [ Time Frame: Day 1 (Baseline), Day 15, Day 29, Day 43, Day 57, Day 71, Day 85, and Day 113 ]measured by urine testing for microalbuminuria/proteinuria
- Efficacy of ambrisentan in improving nociception/pain [ Time Frame: Day 1 (Baseline) through the 12 week treatment period ]assessment of pain diaries/questionnaires
- Efficacy of ambrisentan in improving nociception/pain [ Time Frame: Day 1 (Baseline) through the 12 week treatment period ]assessment of adverse events

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Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- SS or Sβo-thalassemia
- Age 18-65 years
- 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
- Subjects can have Stage 1, II, or III chronic kidney disease (CKD)
- Subjects can be on hydroxyurea, ACE inhibitors (ACEi), or angiotensin receptor blockers (ARBs) for a period of 3 months or greater
- 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:
- Other genotypes of SCD
- History of renal transplant
- Chronic kidney disease (Stage IV and V including patients on hemo dialysis or peritoneal dialysis)
- Patients on chronic transfusion therapy
- Uncontrolled/poorly controlled hypertension or history of hypertension pre-dating proteinuria or
- Known history of HIV, Hepatitis C, and/or diabetes
- Peripheral edema
- History of congestive heart failure or pulmonary edema
- Recent history of coronary artery disease
- Pregnant or breast feeding
- Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) >3-fold upper limit of normal
- Albumin <2.5 gm/dl
- Hemoglobin < 6 gm/dL
- 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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02712346
United States, Georgia | |
Augusta University | |
Augusta, Georgia, United States, 30912 |
Principal Investigator: | Abdullah Kutlar, MD | Augusta University |
Responsible Party: | Abdullah Kutlar, Professor of Medicine, Augusta University |
ClinicalTrials.gov Identifier: | NCT02712346 |
Other Study ID Numbers: |
Endothelin 5U01HL117684 ( U.S. NIH Grant/Contract ) |
First Posted: | March 18, 2016 Key Record Dates |
Last Update Posted: | April 2, 2020 |
Last Verified: | April 2020 |
Sickle Cell Anemia Sickle Cell Thalassemia Sickle Beta Thalassemia Proteinuria Sickle nephropathy |
Anemia, Sickle Cell Anemia Hematologic Diseases Anemia, Hemolytic, Congenital Anemia, Hemolytic |
Hemoglobinopathies Genetic Diseases, Inborn Ambrisentan Antihypertensive Agents |