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

NCT01316796 | Completed Phase 1 FDA Drug

• 2 other identifiers: 11012111-H-0121
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Sickle Cell Anemia; Sickle Cell Disease; Chronic Hemolytic Disorders

Keywords

Sickle Cell Disease; Hemolysis; Anemia; Nitric Oxide; Blood Flow; Leg Ulcer; Sickle Cell Anemia; Thalassemia; Hemolytic Blood Disorder

Outcome Measures

Primary Outcomes (2)

• Evaluate topical sodium nitrite cream's safety and tolerability in patients with sickle cell disease or other hemolytic disorders and chronic leg ulcers.

• Determine the optimal concentration of topical nitrite cream that is tolerated.

Secondary Outcomes (4)

• Determine whether changes of local temperature correlates with ulcer appearance, modification, or healing.

• Determine whether topical nitrite therapy changes regional blood flow to the affected skin area and surrounding.

• Determine whether it shows preliminary evidence for accelerating wound healing.

• Determine the pharmacokinetics of topical sodium nitrite cream and methemolglobin profile in patients with sickle cell disease.

Interventions

Sodium Nitrite Cream DRUG

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Herrick JB. Peculiar elongated and sickle-shaped red blood corpuscles in a case of severe anemia. 1910. Yale J Biol Med. 2001 May-Jun;74(3):179-84. No abstract available.

  PMID: 11501714 BACKGROUND

• Akinyanju O, Akinsete I. Leg ulceration in sickle cell disease in Nigeria. Trop Geogr Med. 1979 Mar;31(1):87-91.

  PMID: 483376 BACKGROUND

• Koshy M, Entsuah R, Koranda A, Kraus AP, Johnson R, Bellvue R, Flournoy-Gill Z, Levy P. Leg ulcers in patients with sickle cell disease. Blood. 1989 Sep;74(4):1403-8.

  PMID: 2475188 BACKGROUND

• Minniti CP, Gorbach AM, Xu D, Hon YY, Delaney KM, Seidel M, Malik N, Peters-Lawrence M, Cantilena C, Nichols JS, Mendelsohn L, Conrey A, Grimes G, Kato GJ. Topical sodium nitrite for chronic leg ulcers in patients with sickle cell anaemia: a phase 1 dose-finding safety and tolerability trial. Lancet Haematol. 2014 Dec 1;1(3):e95-e103. doi: 10.1016/s2352-3026(14)00019-2.

  PMID: 25938131 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell; Hemolysis; Anemia; Leg Ulcer; Thalassemia

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Matthew M Hsieh, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH

Study Record Dates

• First Submitted: March 15, 2011
• First Posted: March 16, 2011
• Study Start: March 15, 2011
• Primary Completion: September 18, 2015
• Study Completion: October 12, 2018
• Last Updated: October 22, 2018

Record last verified: 2018-10-12

Locations

US (1)