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The Role of Endothelin-1 in Sickle Cell Disease

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ClinicalTrials.gov Identifier: NCT02712346
Recruitment Status : Active, not recruiting
First Posted : March 18, 2016
Last Update Posted : July 17, 2019
Sponsor:
Collaborators:
Gilead Sciences
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Abdullah Kutlar, Augusta University

Study Description
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Brief 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.

Condition or disease Intervention/treatment Phase
Sickle Cell Anemia Drug: Ambrisentan Drug: Placebo Phase 1

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Study Design
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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
Estimated Study Completion Date : November 30, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Ambrisentan

Arms and Interventions
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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
 Drug: Placebo
One inactive pill daily for twelve weeks
Other Name: "Sugar Pill"


Outcome Measures
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Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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

  2. 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

  3. Efficacy of ambrisentan in decreasing inflammation [ Time Frame: Day 1 (Baseline) through Day 113 ]
    measurement of inflammatory markers in blood

  4. 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

  5. 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)

  6. 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

  7. 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

  8. Efficacy of ambrisentan in improving nociception/pain [ Time Frame: Day 1 (Baseline) through the 12 week treatment period ]
    assessment of pain diaries/questionnaires

  9. Efficacy of ambrisentan in improving nociception/pain [ Time Frame: Day 1 (Baseline) through the 12 week treatment period ]
    assessment of adverse events


Eligibility Criteria
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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
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
Contacts and Locations
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Information from the National Library of Medicine

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


Locations
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United States, Georgia
Augusta University
Augusta, Georgia, United States, 30912
Sponsors and Collaborators
Augusta University
Gilead Sciences
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Abdullah Kutlar, MD Augusta University
More Information
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Responsible Party: Abdullah Kutlar, Professor of Medicine, Augusta University
ClinicalTrials.gov Identifier: NCT02712346     History of Changes
Other Study ID Numbers: Endothelin
5U01HL117684 ( U.S. NIH Grant/Contract )
First Posted: March 18, 2016    Key Record Dates
Last Update Posted: July 17, 2019
Last Verified: July 2019
Keywords provided by Abdullah Kutlar, Augusta University:
Sickle Cell Anemia
Sickle Cell Thalassemia
Sickle Beta Thalassemia
Proteinuria
Sickle nephropathy
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Anemia
Hematologic Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
 Hemoglobinopathies
Genetic Diseases, Inborn
Ambrisentan
Antihypertensive Agents