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.
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.
Brief Title
Topical Sodium Nitrite in Sickle Cell Disease and Leg Ulcers
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 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
Completion Date
Completion Date Type
Actual
Conditions
Sickle Cell Disease
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)
* 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)
Inclusion 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
* 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
Gender
All
Gender Based
false
Keywords
Sickle cell disease
sodium nitrite
wound healing
Ulcer
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02863068
Org Class
Other
Org Full Name
Montefiore Medical Center
Org Study Id
2016-6015
Overall Status
Terminated
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase II Study of Topical Sodium Nitrite in Patients With Sickle Cell and Leg Ulcers
Primary Outcomes
Outcome Description
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.
Outcome Measure
Assessment of Tolerability (Methemoglobin Level)
Outcome Time Frame
Baseline through last available measurement, up to 10 weeks
Outcome Description
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.
Outcome Measure
Change in Total Ulcerated Surface Area
Outcome Time Frame
From Baseline through last study visit at 10 weeks
Outcome Description
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.
Outcome Measure
Change in Ulcer Pain
Outcome Time Frame
From Baseline through last study visit at 10 weeks
Outcome Description
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.
Outcome Measure
Number of Participants With Total Ulcerated Surface Area Reduction
Outcome Time Frame
From Baseline through last study visit at 10 weeks
Secondary Outcomes
Outcome Description
Hydroxyurea effect on Assessment of Tolerability, as determined by the change in Methemoglobin level, was conducted to evaluate the effect of hydroxyurea in combination with the topical sodium nitrite or placebo. Samples were collected and Methemoglobin levels were measured by co-oximetry. Study outcomes between participants with use of ("HU") and non-use of ("No HU") hydroxyurea are summarized as an increased or decreased percentage by study arm and analyzed using Wilcoxon-Mann-Whitney statistical testing.
Outcome Time Frame
From Baseline through last study visit at 10 weeks
Outcome Measure
Hydroxyurea Effect on Assessment of Tolerability
Outcome Description
Hydroxyurea effect on Change in Total Ulcerated Surface Area was conducted to evaluate the effect of hydroxyurea in combination with the topical sodium nitrite or placebo. 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). Study outcomes between participants with use of ("HU") and non-use of ("No HU") hydroxyurea are summarized by study arm as an increase or decrease in total ulcerated surface area in cm\^2 and analyzed using Wilcoxon-Mann-Whitney and Fisher Exact statistical testing. 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 (with or without Hydroxyurea).
Outcome Time Frame
From Baseline through last study visit at 10 weeks
Outcome Measure
Hydroxyurea Effect on Change in Total Ulcerated Surface Area
Outcome Description
Hydroxyurea effect on change in Ulcer Pain was conducted to evaluate the effect of hydroxyurea in combination with the topical sodium nitrite or placebo. Ulcer pain assessments were conducted using the Visual Analog Scale (VAS). The VAS is used 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." Study outcomes between participants with use of ("HU") and non-use of ("No HU") hydroxyurea are summarized by study arm as an increase or decrease in ulcer pain and analyzed using Wilcoxon-Mann-Whitney statistical testing. Negative results are indicative of a decrease in group median ulcer pain from baseline and positive results are indicative of an increase in group median ulcer pain from baseline (with or without Hydroxyurea).
Outcome Time Frame
From Baseline through last study visit at 10 weeks
Outcome Measure
Hydroxyurea Effect on Change in Ulcer Pain
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Caterina Minniti
Investigator Email
caterina.minniti@einsteinmed.org
Investigator Phone