ClinicalTrials.gov
ClinicalTrials.gov Menu

Topical Sodium Nitrite in Sickle Cell Disease and Leg Ulcers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02863068
Recruitment Status : Recruiting
First Posted : August 11, 2016
Last Update Posted : October 4, 2017
Sponsor:
Collaborator:
Food and Drug Administration (FDA)
Information provided by (Responsible Party):
Caterina Minniti, Montefiore Medical Center

Brief Summary:

The investigators propose a Phase II study, prospective and placebo controlled, 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.


Condition or disease Intervention/treatment Phase
Sickle Cell Disease Drug: Topical Sodium Nitrite Other: Placebo Phase 2

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 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


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase II Study of Topical Sodium Nitrite in Patients With Sickle Cell and Leg Ulcers
Actual Study Start Date : July 1, 2017
Estimated Primary Completion Date : June 30, 2019
Estimated Study Completion Date : June 30, 2020


Arm Intervention/treatment
Placebo Comparator: control
patients will receive placebo and standard of care
Other: Placebo
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.

Experimental: topical sodium nitrite
patients will receive 2% topical sodium nitrite cream and standard of care
Drug: Topical Sodium Nitrite
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.




Primary Outcome Measures :
  1. Assessment of tolerability [ Time Frame: 10 Weeks ]
    The investigators will assess if the application of study cream is well tolerated by subjects. The frequency of each adverse event as per CTCAE v4.0 will be tabulated. To compare the safety of prolonged (10 weeks) treatments between the experimental treatment and placebo group, the investigators will apply non-parametric a Mann-Whitney test on the number of adverse events.

  2. Ulcer size reduction [ Time Frame: 10 Weeks ]
    Effect sizes of the treatment on the ulcer size reduction will be determined by differences in response rates or odds-ratios, and the 95% CI's will accordingly be estimated. To test if topical sodium nitrite accelerates wound healing, as defined by >25% improvement over placebo arm, the investigators will apply Chi-square test. Logistic regression models will be applied if inclusion of confounding variables deems necessary. The investigator will also test if declines of weekly-measured absolute ulcer size on a continuous scale over the study period will be different between the two groups by applying mixed effects linear models for analysis of repeated-measure outcomes.

  3. Ulcer pain reduction [ Time Frame: 10 Weeks ]
    Effect sizes of the treatment on the pain reduction will be determined by differences in response rates or odds-ratios, and the 95% CI's will accordingly be estimated. To test if topical sodium nitrite decreases pain at the wound site>20% over placebo, the investigators will apply Chi-square test. Logistic regression models will be applied if inclusion of confounding variables deems necessary. The investigators will also test if declines of weekly-measured absolute pain VAS scores on a continuous scale over the study period will be different between the two groups by applying mixed effects linear models for analysis of repeated-measure outcomes.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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)


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02863068


Contacts
Contact: Caterina Minniti, M.D. 718-920-4180 cminniti@montefiore.org

Locations
United States, New York
Montefiore Medical center Recruiting
The Bronx, New York, United States, 10467
Contact: Caterina P Minniti, M.D.    718-920-4180    cminniti@montefiore.org   
United States, Pennsylvania
University Of Pittsburgh Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15261
Contact: Gregory J Kato, M.D.    412-648-3017    katogj@upmc.edu   
Sponsors and Collaborators
Montefiore Medical Center
Food and Drug Administration (FDA)
Investigators
Principal Investigator: Caterina Minniti, M.D. Montefiore Medical Center

Publications of Results:
Responsible Party: Caterina Minniti, Professor, Montefiore Medical Center
ClinicalTrials.gov Identifier: NCT02863068     History of Changes
Other Study ID Numbers: 2016-6015
R01FD005729-01 ( U.S. FDA Grant/Contract )
First Posted: August 11, 2016    Key Record Dates
Last Update Posted: October 4, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Caterina Minniti, Montefiore Medical Center:
Sickle cell disease
sodium nitrite
wound healing
Ulcer

Additional relevant MeSH terms:
Anemia, Sickle Cell
Leg Ulcer
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Skin Ulcer
Skin Diseases