Topical Sodium Nitrite in Sickle Cell Disease and Leg Ulcers

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 and randomize
them to be 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 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

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 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 2.5%)

- 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 +) 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 (acetaminophen)
Phenylhydrazine Rasburicase Sulfonamides (sulfacetamide, sulfamethoxazole, sulfanilamide,
sulfapyridine)