A Phase 1 interventional study of Sodium Nitrite Cream in Sickle Cell Anemia, Sickle Cell Disease and Chronic Hemolytic Disorders, sponsored by National Heart, Lung, and Blood Institute (NHLBI). Completed at 1 site in United States. Open to participants aged 18 Years to 99 Years. Per ClinicalTrials.gov, last updated 2018-10-22.
Sponsored by National Heart, Lung, and Blood Institute (NHLBI) · Phase 1, Interventional, and Treatment
Background:
Objectives:
Eligibility:
Design:
Leg ulcerations have long been identified as a serious and debilitating complication of SCD and even the first SCD patient described in North America in 1910 had leg ulcerations. The prevalence varies, being low before 10 years of age, and in genotypes other than SS, and it is influenced by geographical location, with an occurrence as high as 75 percent of SS patients in Jamaica, and 8-10 percent in North America. The etiology of chronic ulcers in SCD and other hemolytic disorders is unknown, mechanical obstruction by dense sickled red cell, increased venous pressure, bacterial infections, abnormal autonomic control with excessive vasoconstriction when in the dependent position, degree of anemia with decrease in oxygen carrying capacity, and in situ thrombosis, have all been proposed as potential contributing factors. Recent studies have reported increased incidence of leg ulcers in patients with pulmonary hypertension. Our group has pioneered the notion of an association between the hemolytic phenotype and leg ulcers. Current treatment options for leg ulcerations, including antibiotics, compression bandages, dressing changes, Unna boots, silver and zinc oxide gauze, skin grafts and maggot therapy rely mostly on bacterial containment, stimulation of granulation formation and decrease of venostasis. Pathological changes in the microcirculation associated with ulceration are not addressed. Nitric oxide metabolism has been the focus of our branch research over the past several years. We know that it mediates essential biological processes, including vasodilatation, wound healing, and angiogenesis and has antimicrobial activity. Moreover, NO has an antiplatelet effect and influences several growth factors involved in endothelial homeostasis.
We propose a Phase I study of a topical cream containing escalating doses of sodium nitrite, a local donor of NO when in the presence of heme, as a novel approach to the therapy for chronic leg ulcers in hemolytic disorders. The primary objectives are to evaluate topical sodium nitrite cream s safety and tolerability in patients with sickle cell disease or other hemolytic disorders and chronic leg ulcers and to determine the optimal concentration of the study drug that is tolerated. Subjects will be treated at the Clinical Center for 4 weeks.
Potential benefit will be a durable resolution or improvement of the leg ulcer. Possible side effects include hypotension and methemoglobinemia, secondary to sodium nitrite absorption for the ulcerated skin. Safety measures will be used and pharmacokinetics analysis of sodium nitrite absorption in this setting will be obtained. As a secondary endpoint, we will study the biology of leg ulcer formation in patients with hemolytic disorders, its pathological appearance on a skin biopsy, and the role of microvascular changes in its formation and (possibly) resolution. Sophisticated and novel studies of blood flow and temperature changes during sodium nitrite application, as well as macrovascular appearance on MRI will allow for a better understanding of ulcer formation. This may lead to novel approaches to the therapy of ulcer in hemolytic and non-hemolytic disorders, such as diabetes and decubitus ulceration.
1,733 studies on the registry are indexed under Anemia; 246 are open to participants now.
This study's enrollment of 28 is below the median of 94 across 1,291 interventional studies indexed under Anemia.
Browse Anemia studies →National Heart, Lung, and Blood Institute (NHLBI) is the lead sponsor of 1,117 studies on the registry; 71 are open to participants now.
Of its 57 completed or terminated interventional studies of FDA-regulated products, 49 (86%) have results posted.
Counted across the registry records on this site, refreshed daily.
Each subject must meet all of the following inclusion criteria during the screening process in order to participate in the study:
EXCLUSION CRITERIA:
Subjects meeting any of the following criteria during baseline evaluation will be excluded from entry into the study:
The following list of drugs and agents may cause methemoglobinemia and should be avoided while on this study:
Sulfonamides (sulfacetamide, sulfamethoxazole, sulfanilamide, sulfapyridine)
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.
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.
This study is completed, as verified in Oct 2018. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
National Heart, Lung, and Blood Institute (NHLBI)