Clinical trial NCT02863068: Topical Sodium Nitrite in Sickle Cell Disease and Leg Ulcers
Official title: A Phase II Study of Topical Sodium Nitrite in Patients With Sickle Cell and Leg Ulcers
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Sickle Cell Disease
Keywords: Sickle cell disease
sodium nitrite
wound healing
Ulcer
Lead sponsor: Montefiore Medical Center
Sponsor class: OTHER
Collaborators: name: Duke University
First posted: 2016-08-11
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigators are conducting a Phase II prospective and placebo controlled study of a topical cream containing sodium nitrite compared to the current standard of care. Sodium nitrite is a local donor of nitric oxide, which is known to improve blood flow and decrease bacterial load in the ulcer bed. The primary objectives are to evaluate the safety of topical sodium nitrite cream treatment in patients with sickle cell disease and chronic leg ulcers and to determine its effectiveness in accelerating the healing process and decreasing the pain associated with ulceration.

Potential benefit will be a durable resolution or improvement of the leg ulcer and its associated pain. Possible side effects include decreased blood pressure and methemoglobinemia, secondary to sodium nitrite absorption through the ulcerated skin.

Funding source FDA OOPD.

Detailed description: 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.

Investigators are planning to enroll fifty patients with sickle cell disease to be randomized and treated twice a week with sodium nitrite cream or a placebo for ten weeks. The following events will be compared in treatment and placebo arms: a) changes in blood pressure; b) changes in pulse oximetry; c) changes in methemoglobin levels; d) any adverse events; e) rate of sickle cell disease (SCD) related complications; f) changes in biomarkers of inflammation and other laboratory data such as complete blood count and chemistries.

In order to determine if topical sodium nitrite accelerates wound healing and decreases pain at the wound site compared to placebo in patients receiving similar levels of wound care, investigators will a) accurately measure and photograph ulcers at baseline, after a two week run-in period and at predefined time points during the study and compare treatment arm to placebo; b) pain scores at wound sites will be recorded and compared for the two groups, c) Investigators will calculate opioid intake in the two arms and d) quality of life measures before and at the end of the trial

Eligibility criteria: Inclusion Criteria:

* Subjects must have a diagnosis of sickle cell disease (SS, SC, Sß-thalassemia, SD, SOArab)
* Have one or more ulcers of the one or both leg or foot
* Total surface area of leg ulcer(s) that will receive treatment must be no larger than 100 cm2
* No history of congenital methemoglobinemia
* Have documented normal Glucose-6-Phosphate Dehydrogenase (G6PD) activity

Exclusion Criteria:

* 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 3.5% on two different occasions)
* Patients who are currently enrolled in any other investigational drug study (this does not include observational or natural history protocols)
* Use of Phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil, 4 days prior to screening
* Pregnant women - urine or serum Human chorionic gonadotropin (hCG)+ 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, propellant, fuel additive) Nitrofurantoin (furadantin) Pyridium (phenazopyridine) Phenacetin Phenylhydrazine Rasburicase Sulfonamides (sulfacetamide, sulfamethoxazole, sulfanilamide, sulfapyridine)

Primary outcomes:
measure: Assessment of Tolerability (Methemoglobin Level)
timeFrame: Baseline through last available measurement, up to 10 weeks
measure: Change in Total Ulcerated Surface Area
timeFrame: From Baseline through last study visit at 10 weeks
measure: Change in Ulcer Pain
timeFrame: From Baseline through last study visit at 10 weeks
measure: Number of Participants With Total Ulcerated Surface Area Reduction
timeFrame: From Baseline through last study visit at 10 weeks
Secondary outcomes:
measure: Hydroxyurea Effect on Assessment of Tolerability
timeFrame: From Baseline through last study visit at 10 weeks
measure: Hydroxyurea Effect on Change in Total Ulcerated Surface Area
timeFrame: From Baseline through last study visit at 10 weeks
measure: Hydroxyurea Effect on Change in Ulcer Pain
timeFrame: From Baseline through last study visit at 10 weeks
Other outcomes:
Locations:
city: Bronx
country: United States
facility: Montefiore Medical Center - Albert Einstein College of Medicine
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: Montefiore Medical Center
name: Caterina Minniti, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.