Blockade of mini-TrpRS for treatment of diabetic foot syndrome: A Prospective open-label phase 1a/1b randomized placebo-controlled trial.
Townsville University Hospital
112 participants
Jul 1, 2021
Interventional
Conditions
Summary
The study aims to demonstrate that D-Tryptophan is safe and has pharmacokinetic tolerability and its therapy is associated with clinically significant reductions in biological markers of inflammation, wound area, and healing time compared to placebo in type 2 diabetic patients with diabetic foot ulcer (DFU).The study will have two phases, phase 1a (single ascending dose, SAD) being the single-dose escalation part. Based on the results of the Phase 1a trial, the study will be followed by phase 1b dose expansion part (multiple ascending doses, MAD) of the study, which will involve an increase in the number of participants and a treatment period of 12 weeks compared to placebo (control arm). study participants inlcude; 1.Subjects greater than or equal to 18 years of age diagnosed with type 2 diabetes on diet only or any diabetic medication regime. 2. Existing diabetes index foot ulcer grade A1 or higher according to the University of Texas Wound Classification System of Diabetic Foot Ulcers on the day of study inclusion. The study will be conducted on subjects attending High Risk Diabetes Foot Clinic at the Townsville Hospital and Kirwan Community Health after obtaining ethics approval and acquiring informed consent.
Eligibility
Inclusion Criteria2
- Subjects greater than or equal to 18 years of age diagnosed with type 2 diabetes on diet only or any diabetic medication regime.
- Existing diabetes index foot ulcer grade A1 or higher according to the University of Texas Wound Classification System of Diabetic Foot Ulcers on the day of study inclusion. A foot ulcer is defined as any full-thickness skin defect existing for at least 14 days. In patients with multiple diabetic foot ulcers, the index foot ulcer is defined as the foot ulcer with the largest wound area at the time of inclusion
Exclusion Criteria13
- Type 1 Diabetes.
- Current index foot ulcer of any non-diabetic pathophysiology (e.g. rheumatoid, radiation-related, vasculitis-related, calciphylaxis, or dystrophic calcinosis cutis, etc.).
- Any major surgery up to 6 months before the day of enrolment or any planned surgery before study completion, including any major surgical intervention for the diabetic foot ulcer.
- Significant medical conditions that potentially impair wound healing and/or alter the concentration of serum immune markers including hepatic, respiratory or cardiac failure, aplastic anemia, autoimmune diseases (e.g., Lupus erythematosus, scleroderma, etc.), chronic inflammatory diseases (e.g., inflammatory bowel disease, inflammatory or rheumatoid arthritis, etc.) and any active malignancies including cancerous or pre-cancerous lesions in the ulcer area other than basal cell carcinoma.
- Any concomitant medication which could potentially alter the concentration of serum immune markers during the study including systemic cortocosteroids, immunosuppressants, chemotherapeutic agents, growths factor products, etc.
- Skin and dermal substitutes within 30 days before study enrolment.
- Enzymatic debridement treatment.
- Active Charcot's foot as determined by clinical and radiographic examination.
- Significant renal impairment (eGFR < 30 ml/min).
- Pregnancy, lactation or child-bearing potential. Women must be either of non-childbearing potential as defined in the protocol or must have a negative pregnancy test on the day of study inclusion or randomization and agree to use an adequate method of contraception as defined in the protocol for at least until two weeks after taking the last dose of study medication. Also, men who take part in this study should genuinely not plan to get their partners pregnant (no active family planning) while participating in this study and until 14 days after taking the last dose of study medication.
- Participation in any other clinical trial.
- Inability to comply with study protocol.
- Any current or new contraindication, special warning, precaution or other patient safety-related concern relevant to the patient at the time of enrolment as listed in the current product information.
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Interventions
To demonstrate that D-Tryptophan is safe and has pharmacokinetic tolerability and its therapy is associated with clinically significant reductions in biological markers of inflammation, wound area, and healing time compared to placebo in type 2 diabetic patients with diabetic foot ulcer (DFU). The study will have two phases, phase 1a (single ascending dose, SAD) being the single-dose escalation part. Based on the results of the Phase 1a trial, the study will be followed by phase 1b dose expansion part (multiple ascending doses, MAD) of the study, which will involve an increase in the number of participants and a treatment period of 12 weeks compared to placebo (control arm). Phase 1a (SAD): one single dose (oral) in the ratio 3:1 ; drug (n=6) or placebo (n=2) in four cohorts. dosage: 200mg, 400mg, 800mg and 1200mg Phase 1b (MAD): for this dose (oral drug) expansion part of the study; 20 in each group will be treated, totaling 80 participants for 12 weeks; 200mg (once daily for 12 weeks), 400mg (once daily, for 12 weeks), 800mg (twice 400mg per day, for 12 weeks) and 1200mg (thrice 400mg per day for 12 weeks) Dosage Adherence: Study participants will be requested to bring trial drug bottles and study nurse will verify adherence rates and document Standard Wound Care: The same standard of wound care will be provided to all enrolled patients throughout the study. Podiatrists will manage foot ulcers with a particular interest in wound healing and compression therapy. The subjects will self-dress their wounds three days a week and will be reviewed by a podiatrist or clinician on a fortnightly basis (Patient Visit 1– Patient Visit 7). Instructions on how to self-dress wounds will be given to patients and documented in the “additional comments section” of the “Queensland Health High-Risk Foot Form” for later comparison with what the patients did at home, as documented in their patient diaries. Dry necrotic lesions will be hydrated to promote a moist wound environment, encouraging autolytic debridement and cell migration. An atraumatic dressing and a non-adherent absorbent pad will be applied as a secondary dressing. After autolytic debridement, a conformable silver poly-membrane will be applied and retained with a light tubular support bandage. If the wound is infected, antibiotics will be administered based on microscopy, culture, and sensitivity results following deep wound swabs and blood cultures. Any antibiotics administered will also be documented in the concomitant medication section of the CRF.
Locations(1)
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ACTRN12621000120875