The Role of Endothelin-1 in Sickle Cell Disease

NCT02712346 | Completed Phase 1

• 2 other identifiers: Endothelin5U01HL117684
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Sickle Cell Anemia

Keywords

Sickle Cell Anemia; Sickle Cell Thalassemia; Sickle Beta Thalassemia; Proteinuria; Sickle nephropathy

Outcome Measures

Primary Outcomes (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

  Day 1 (Baseline) through Day 113

Secondary Outcomes (9)

• Efficacy of ambrisentan in improving kidney function in patients with sickle cell disease measured by blood

  Day 1 (Baseline), Day 15, Day 29, Day 57, Day 85, and Day 113

• Efficacy of ambrisentan in decreasing TRJ velocity

  Day 1 (Baseline) and at the end of the 12 week treatment period

• Efficacy of ambrisentan in decreasing inflammation

  Day 1 (Baseline) through Day 113

• Efficacy of ambrisentan in improving micro-circulation

  Day 1 (Baseline) and at the end of the 12 week treatment period

• Efficacy of ambrisentan in improving macro-circulation

  Day 1 (Baseline), and at the end of the 12 week treatment period

Study Arms (2)

Treatment

EXPERIMENTAL

Ambrisentan 5 mg PO daily

Drug: Ambrisentan

Placebo

PLACEBO COMPARATOR

One inactive pill PO daily

Drug: Placebo

Interventions

Ambrisentan DRUG

Ambrisentan 5 milligrams a day or a placebo (sugar pill) for twelve weeks

Also known as: Letairis

Treatment

Placebo DRUG

One inactive pill daily for twelve weeks

Also known as: "Sugar Pill"

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Augusta University: lead
• Gilead Sciences: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Augusta University

Augusta, Georgia, 30912, United States

Location

Related Publications (1)

• Obadina M, Wilson S, Derebail VK, Little J. Emerging Therapies and Advances in Sickle Cell Disease with a Focus on Renal Manifestations. Kidney360. 2023 Jul 1;4(7):997-1005. doi: 10.34067/KID.0000000000000162. Epub 2023 May 31.

  PMID: 37254256 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell; Proteinuria

Interventions

ambrisentan; Sugars

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Carbohydrates

Study Officials

• Abdullah Kutlar, MD

  Augusta University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: October 2, 2015
• First Posted: March 18, 2016
• Study Start: September 1, 2015
• Primary Completion: May 30, 2019
• Study Completion: November 30, 2019
• Last Updated: April 2, 2020

Record last verified: 2020-04

Locations

US (1)