Topical Sodium Nitrite in Sickle Cell Disease and Leg Ulcers

NCT02863068 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 2016-6015
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 3

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.

Conditions

Sickle Cell Disease

Keywords

Sickle cell disease; sodium nitrite; wound healing; Ulcer

Outcome Measures

Primary Outcomes (4)

• Assessment of Tolerability (Methemoglobin Level)

  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.

  Baseline through last available measurement, up to 10 weeks

• Change in Total Ulcerated Surface Area

  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.

  From Baseline through last study visit at 10 weeks

• Change in Ulcer Pain

  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.

  From Baseline through last study visit at 10 weeks

• Number of Participants With Total Ulcerated Surface Area Reduction

  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.

  From Baseline through last study visit at 10 weeks

Secondary Outcomes (3)

• 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

Study Arms (2)

control

PLACEBO COMPARATOR

patients will receive placebo and standard of care

Other: Placebo

topical sodium nitrite

EXPERIMENTAL

patients will receive 2% topical sodium nitrite cream and standard of care

Drug: Topical Sodium Nitrite

Interventions

Topical Sodium Nitrite DRUG

Subjects will have 0.1 cm of 2% sodium nitrite cream applied per 1 cm2 of the total ulcerated area. Areas will be rounded to the nearest 1 cm2. If a subject has more than one ulcer, all of them will be treated with either "study cream" in this intervention.

topical sodium nitrite

Placebo OTHER

Subjects will have Placebo applied to total ulcerated area. If a subject has more than one ulcer, all of them will be treated with placebo in this intervention.

control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• caterina P minniti: lead
• Duke University: collaborator

Study Sites (3)

Montefiore Medical Center - Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15260, United States

Location

Related Publications (1)

• 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.

  PMID: 25938131 BACKGROUND

MeSH Terms

Conditions

Anemia, Sickle Cell; Ulcer

Interventions

Sodium Nitrite

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Nitrites; Nitrous Acid; Nitrogen Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

Due to the early termination of the study, enrollment in the clinical trial did not reach the target number of participants needed to produce statistically reliable results.

Results Point of Contact

• Title: Dr. Caterina Minniti
• Organization: Albert Einstein College of Medicine

bloodconsultant@gmail.com

240-498-8684

Study Officials

• Caterina Minniti, M.D.

  Montefiore Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 16, 2016
• First Posted: August 11, 2016
• Study Start: April 6, 2018
• Primary Completion: November 24, 2023
• Study Completion: November 24, 2023
• Last Updated: May 7, 2025
• Results First Posted: May 7, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)