A Phase II Study of Topical Sodium Nitrite in Patients With Sickle Cell and Leg Ulcers
Overview
- Phase
- Phase 2
- Intervention
- Placebo
- Conditions
- Sickle Cell Disease
- Sponsor
- caterina P minniti
- Enrollment
- 18
- Locations
- 3
- Primary Endpoint
- Assessment of Tolerability (Methemoglobin Level)
- Status
- Terminated
- Last Updated
- 12 months ago
Overview
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
Investigators
caterina P minniti
Professor
Montefiore Medical Center
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)
Arms & Interventions
control
patients will receive placebo and standard of care
Intervention: Placebo
topical sodium nitrite
patients will receive 2% topical sodium nitrite cream and standard of care
Intervention: Topical Sodium Nitrite
Outcomes
Primary Outcomes
Assessment of Tolerability (Methemoglobin Level)
Time Frame: Baseline through last available measurement, up to 10 weeks
Assessment of tolerability was determined by evaluating the change in methemoglobin level from baseline through the end of study at week 10. Samples were collected and Methemoglobin levels were measured by co-oximetry Results are summarized by study arm using basic descriptive statistics and expressed as a percentage of the total hemoglobin in the sample.
Change in Total Ulcerated Surface Area
Time Frame: From Baseline through last study visit at 10 weeks
Change in total ulcerated surface area from baseline was assessed through the last study visit at 10 weeks. Surface area measurements of the ulcer were obtained and photographed with defined lighting, distance, exposure, and camera type. Total ulcerated surface area measurements were obtained using digital planimetry and measuring the longest length and widest width of the ulcer(s). Results are summarized by study arm using basic descriptive statistics and reported in cm\^2. Negative results are indicative of a reduction in group median total ulcerated surface area from baseline and positive results are indicative of an increase in group median total ulcerated surface area from baseline.
Change in Ulcer Pain
Time Frame: From Baseline through last study visit at 10 weeks
Change in Ulcer Pain from baseline through the last study visit at 10 weeks were assessed using the Visual Analog Scale (VAS). The VAS is a widely used tool to quantify subjective pain perception over time and in this study was used to determine the efficacy of the topical sodium nitrite. Participants were asked to mark a point on a line indicating the severity of their pain on a 0-10 scale, with "0" representing "No pain" and "10" representing the "Worst possible pain." A decrease in VAS score is indicative of a reduction in ulcer pain. Scores were summarized by study arm using basic descriptive statistics.
Number of Participants With Total Ulcerated Surface Area Reduction
Time Frame: From Baseline through last study visit at 10 weeks
The number of participants who achieved an objective reduction in total surface area of the ulcer of \>= 25% from baseline is summarized and reported as a dichotomous ("No" or "Yes") variable.
Secondary Outcomes
- Hydroxyurea Effect on Assessment of Tolerability(From Baseline through last study visit at 10 weeks)
- Hydroxyurea Effect on Change in Total Ulcerated Surface Area(From Baseline through last study visit at 10 weeks)
- Hydroxyurea Effect on Change in Ulcer Pain(From Baseline through last study visit at 10 weeks)