Topical Sodium Nitrite for Chronic Leg Ulcers in Adult Patients With Blood Disorders

• Status: Completed
• Trial end date: 2018-10-12
• Target enrollment: 0
• Participant gender: All

Summary

Background:

• Chronic leg ulcers are a complication of many blood disorders such as sickle cell disease, thalassemia, and other red blood cell disorders. In these disorders, red blood cells break down earlier than normal, which researchers suspect may cause or contribute to the development of leg ulcers; however, the exact cause is unknown, and current therapies are not very effective. Researchers are interested in determining if a research cream made with sodium nitrite, a substance that is known to increase blood flow by dilating blood vessels, may speed up the healing of skin ulcers.

Objectives:

• To evaluate the safety and effectiveness of topical sodium nitrite cream as a treatment for chronic leg ulcers in individuals with sickle cell disease or other red blood cell disorders.

Eligibility:

• Individuals at least 18 years of age who have sickle cell disease or another red cell disorder and have had a leg ulcer for more than 4 weeks.

Design:

• Participants will be screened with a physical examination, medical history, blood tests, and an examination of the ulcer, including x-ray of the leg(s) with the ulcer and swabs from the wound.

• Participants will be scheduled for a 5-day inpatient stay at the Clinical Center, with the following procedures:

• Days 1 and 2: Participants will have blood draws, a wound assessment, ultrasound of the affected leg, imaging studies (magnetic resonance imaging and infrared photography), thermo-patch application to monitor temperature changes, measurements of blood flow in the skin, and questionnaires about pain and quality of life. An optional skin biopsy may also be conducted with samples taken near the skin ulcer

• Day 3: Participants will have one ulcer treated with the topical cream. Frequent blood draws will be conducted before application and then regularly for up to 6 hours after application of the cream. Thirty minutes after the research cream is applied, participants will have imaging studies of the treated leg and measurements of pain levels and blood flow.

• Day 4: Participants will have a blood draw and temperature recordings taken.

• Day 5: Participants will have the research cream applied and the same imaging studies as before, and will be discharged for care at home.

• For the following 3 weeks, participants will come to the clinical center twice a week to have the research cream applied to the leg ulcer and tests performed by the study researchers.

• For the fourth and final week, participants will return for additional cream treatment sessions, imaging studies, blood draws, and other tests as directed by the study researchers.

• Study participation will end in the following week (week 5). Subjects will come for a final visit one month after the end of the study.

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

Details

• Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Criteria

• INCLUSION CRITERIA:

Each subject must meet all of the following inclusion criteria during the screening process in order to participate in the study:

• Subjects must have a diagnosis of sickle cell disease (SS, SC, S-beta-thalassemia), other hemoglobinopathies, or hemolytic disorders, such as hereditary spherocytosis.

• Be at least 18 years old.

• Have a leg ulcer of at least 4 weeks (28 days) duration.

• Leg ulcer must be no smaller than 2.5 cm(2) and no larger than 100 cm(2).

• Provide written informed consent.

EXCLUSION CRITERIA:

Subjects meeting any of the following criteria during baseline evaluation will be excluded from entry into the study:

• Exposure to therapeutic nitric oxide, L-arginine, nitroprusside or nitroglycerine within the past 1 week.

• Subjects presenting with clinically diagnosed bacterial infection (e.g., osteomyelitis, pneumonia, sepsis or meningitis).

• Subjects who have a pre-existing methemoglobinemia (more than 2.5 percent), unless the cytochrome b5 reductase (methemoglobin reductase) is within normal limits and the methemoglobin is no greater than 3 percent)

• Patients who are currently enrolled in any other investigational drug study (this does not include observational or natural history protocols).

• Use of PDE5 inhibitors, such as sildenafil, 4 days prior to screening.

• Pregnant women (urine or serum HCG plus) or nursing mothers.

• The following list of drugs and agents may cause methemoglobinemia and should be avoided while on this study:

• Anesthetics (local): Benzocaine, procaine, prilocaine, Anbesol, Orajel

• Antimalarials: chloroquine, primaquine, quinacrine

• Aniline dyes

• Chlorates

• Dapsone

• Diarylsulfonylureas

• Doxorubicin

• Metoclopramide

• Nitric and nitrous oxide

• Nitrobenzenes (shoe and floor polish and in paint solvents)

• Nitroethane (artificial nail remover, propellent, fuel additive)

• Nitrofurantoin (furadantin)

• Pyridium (phenazopyridine)

• Phenacetin (acetaminophen)

• Phenylhydrazine

• Rasburicase

• Sulfonamides (sulfacetamide, sulfamethoxazole, sulfanilamide, sulfapyridine)

• If a subject participant meets exclusion criteria while participating in the trial, then the subject will be removed from the study.