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 : December 16, 2019
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|
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|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Official Title:||A Phase II Study of Topical Sodium Nitrite in Patients With Sickle Cell and Leg Ulcers|
|Actual Study Start Date :||April 6, 2018|
|Estimated Primary Completion Date :||December 30, 2021|
|Estimated Study Completion Date :||June 30, 2022|
Placebo Comparator: control
patients will receive placebo and standard of care
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.
- 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.
- 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.
- 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.
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
|Contact: Caterina Minniti, M.D.||firstname.lastname@example.org|
|United States, New York|
|Montefiore Medical center||Recruiting|
|Bronx, New York, United States, 10467|
|Contact: Caterina P Minniti, M.D. 718-920-4180 email@example.com|
|United States, Pennsylvania|
|University Of Pittsburgh||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15261|
|Contact: Gregory J Kato, M.D. 412-648-3017 firstname.lastname@example.org|
|Principal Investigator:||Caterina Minniti, M.D.||Montefiore Medical Center|