Nitric Oxide Footbath for Treatment of Diabetic Foot Ulcers

NCT04755647 | Completed Phase 1

• 1 other identifier: DFU-CTP-01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate the safety and effectiveness of a nitric oxide releasing solution, delivered as a footbath, to act as an antimicrobial treatment for participants presenting with a diabetic foot ulcer.

Conditions

Diabetic Foot Ulcer

Keywords

nitric oxide; diabetic wounds; diabetic foot ulcer; drug resistent wound

Outcome Measures

Primary Outcomes (7)

• To measure the number of participants discontinued or lost to follow-up in the NORS compared to hypotonic saline in participants with diabetic foot ulcers (DFU)

  Proportion of participants lost-to-follow-up, discontinuing study treatment due to intolerance or adverse events, or initiating new medications or treatments, or leaving/discontinuing the study for any other reason

  28 days

• To measure the severity of adverse events of NORS compared to hypotonic saline in participants with DFU

  Severity as measured by adverse event scale (1-5) and frequency of adverse events that results in discontinuation of the investigative treatment.

  29 days

• To measure the negative changes in laboratory values of NORS compared to hypotonic saline with DFU

  Proportion of negative laboratory changes resulting in discontinuation of investigative treatments.

  29 days

• To measure the negative changes in vital sign during NORS compared to hypotonic saline administration in participants with DFU

  Proportion of subjects with deterioration in vital signs resulting in discontinuation of investigative treatment.

  29 days

• To measure worsening of wound infection during NORS compared to hypotonic saline administration in participants with DFU

  Proportion of subjects with incidence of infection resulting in discontinuation of the investigative treatment.

  29 days

• To measure worsening of wound area during NORS compared to hypotonic saline administration in participants with DFU

  Proportion of subjects with increased wound area resulting in discontinuation of the investigative treatment.

  29 days

• To measure the methemoglobin percent level during NORS compared to hypotonic saline administration in participants withe DFU

  Proportion of subjects with an increase in methemoglobin percent level resulting in discontinuation of the investigative treatment.

  29 days

Secondary Outcomes (5)

• To measure the efficacy of NORS compared to placebo on the change in pathogen load in participants with DFU

  29 days

• To measure the efficacy of NORS compared to placebo on the change in bacterial load (CFU/mL) in participants with DFU

  29 days

• To measure the efficacy of NORS compared to placebo on the reduction of the number of clinical signs of infection in participants with diabetic foot ulcers (DFU)

  29 days

• To measure the efficacy of NORS compared to placebo on the change in wound bacterial microbiota (species) in participants with DFU

  29 days

• To measure the efficacy of NORS compared to placebo on the change in wound area in participants with DFU

  29 days

Study Arms (2)

Nitric Oxide-Releasing Solution (NORS)

EXPERIMENTAL

Five litre foot bath delivery NORS

Drug: Nitric Oxide-Releasing Solution

Saline

PLACEBO COMPARATOR

Five litre foot bath delivery NORS

Drug: Saline solution, hypotonic

Interventions

Nitric Oxide-Releasing Solution DRUG

Active antimicrobial

Nitric Oxide-Releasing Solution (NORS)

Saline solution, hypotonic DRUG

Placebo

Saline

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Non-hospitalized, ambulatory patients with controlled diabetes mellitus as determined by physician diagnosis recorded in the medical record. Diabetes may be treated with insulin, oral hypoglycemic agents or diet alone. Patient glycaemic control (HbA1c) should be less than or equal to 12 % within 2 weeks of enrollment;
• Must be ≥ 19 years of age unless local laws dictate otherwise;
• Participants must be considered reliable, willing and able to give signed informed consent, and sign the informed consent form.
• Participant is willing to be randomized and able to comply with the protocol
• Participants must have either:
• i) 1 or more full thickness ulcers on the foot below the malleoli with a surface area exceeding 0.5 cm2 (50 mm2) after debridement (full thickness means extending through the epidermis and dermis but not involving tendon, bone, or joint capsule); or ii) 1 or more partial thickness ulcers (i.e., do not completely penetrate the dermis) of forefoot or digits; or iii) 1 or more ulcers of the forefoot or digits have granulation tissue at their base.
• Participants must have localized mild infection of at least 1 ulcer that would ordinarily be treated on an outpatient basis. Mild infection of an ulcer is defined by the presence of at least 2 manifestations of inflammation (purulence, erythema, pain, tenderness, warmth, or induration) which is limited to the skin or superficial subcutaneous tissues. If there is more than one ulcer meeting eligibility, the Investigator will determine which ulcer will be followed for the course of the study.
• Mild infection defined by IDSA criteria34:
• i) "Local infection involving only the skin and the subcutaneous tissue (without involvement of deeper tissues and without systemic signs as described below).
• ii) If erythema, must be \>0.5 cm to ≤2 cm around the ulcer. Exclude other causes of an inflammatory response of the skin (e.g., trauma, gout, acute Charcot neuro-osteoarthropathy, fracture, thrombosis, venous stasis)."
• Participants who have been previously treated or are currently under treatment for a localized infection of an ulcer may be enrolled if there has been an inadequate response to treatment and the ulcer is still infected as described above.
• Participants must have a radiograph (appropriate views as determined by the investigator) within the 2 weeks prior to entry showing no evidence of cortical destruction consistent with osteomyelitis in the affected foot.
• Participants must have either:
• i) A palpable dorsalis pedis or posterior tibial pulse in the affected foot; or ii) If the pulse is congenitally absent or not palpable due to edema, a Dopplerable dorsalis pedis or posterior tibial pulse measured at ≥ 30 mm Hg; or iii) If there are no palpable pulses, non Dopplerable pulses, rest pain, or claudication on walking less than one block are present, the patient may be enrolled only if a vascular surgeon has determined that vascular surgery, angioplasty or amputation is not warranted.
• Participants must have no more than a reduced wound area of ≤30% documented by the PI, during the 2 weeks of screening, in which patients received institutional standard of care (SOC)

You may not qualify if:

• Participants with limb threatening infection, extensive cellulitis (≥2 cm beyond the ulcer), lymphangitis, fasciitis, deep tissue infection, an abscess, or other evidence of local complications of infection.
• Participants with symptoms of systemic infection (e.g., severe hyperglycemia, ketoacidosis, azotemia).
• Participants requiring concurrent local or systemic antimicrobials during the study period for any infection, including diabetic foot ulcer.
• Participants who are currently treated by dialysis, awaiting dialysis or who have an estimated glomerular filtration rate of ≤20 mL/min/173 m2.
• Participants who are expected to be unable to care for their ulcer because of hospitalization, vacation, disability, etc. during the study period.
• Participants with known active alcohol or substance abuse within the 6 months preceding study entry.
• Participants who are receiving systemic corticosteroids (in a dose equivalent to ≥ 20 mg of prednisone per day) immunosuppressive radiation therapy, or cytotoxic agents
• Participants who require treatment for a primary or metastatic malignancy (other than squamous or basal cell carcinoma of the skin).
• Participants with a systemically immunocompromising disease, such as acquired immune deficiency syndrome or known human immunodeficiency virus (HIV) positivity.
• Participants who have an unexplained fever or chills during the week prior to enrollment.
• Participants with other conditions considered by the investigator to be reasons for disqualification that may jeopardize patient safety or interfere with the objectives of the trial (e.g., acute illness or exacerbation of chronic illness, lack of motivation, history of poor compliance).
• Women who are breast feeding, pregnant or attempting to become pregnant.

Sponsors & Collaborators

• Sanotize Research and Development corp.: lead

Study Sites (1)

Achilles Foot Health Centre

Vancouver, British Columbia, Canada

Location

MeSH Terms

Conditions

Diabetic Foot

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Scott Schumacher, MD

  Achilles Foot Health Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Packaging will be generic, coded and indistinguishable from placebo.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a single-center, randomized, placebo controlled parallel group,clinical safety study comparing an investigational drug add-on to a placebo control. Up to 40 participants with mildly infected neuropathic or non-neuropathic or neuro-ischemic diabetic foot ulcers will be enrolled.

Study Record Dates

• First Submitted: February 8, 2021
• First Posted: February 16, 2021
• Study Start: February 23, 2021
• Primary Completion: May 20, 2023
• Study Completion: May 20, 2023
• Last Updated: May 31, 2023

Record last verified: 2022-10

Locations

CA (1)