Safety and Efficacy of Stem Cells for Diabetic Foot Ulcer

A Randomized, Double Blind, Placebo Controlled, Phase I/II Study Assessing the Efficacy and Safety of Peri-Ulcer Administration of Wharton-Jelly Mesenchymal Stem Cells in Patients With Non-Healing Diabetic Foot Ulcer

The objective of this clinical trial is to evaluate the effectiveness and safety of Wharton-Jelly mesenchymal stem cells administered around the ulcer site in patients with nonhealing diabetic foot ulcers. The key inquiries it seeks to address include the percentage of patients achieving complete healing/closure of the specified ulcer at any point during the 6-week period, the duration required for the complete closure of the target ulcer, and the nature and occurrence of adverse events (AEs), along with the total number of AEs and the proportion of patients experiencing AEs.

Patients meeting the eligibility criteria will receive either allogeneic mesenchymal stromal cells (MSC) or a placebo. The peri-ulcer injection of umbilical cord MSC or placebo will be administered at multiple locations, around the ulcer. Subsequent follow-up after the administration of umbilical cord MSC or placebo will be conducted to monitor and observe the progress of ulcer healing.

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetic Foot Ulcer
• Intervention / Treatment: Drug: Allogeneic mesenchymal stem cells (MSCs); Drug: Normal Saline

Detailed Description

Research involving MSCs promises new treatments and possible cures for many chronic and debilitating diseases. It has been shown that MSCs could be an effective therapy for many diseases, including CLI, AMI, OA of the knee, LC and DFU. No significant side effects have been reported with allogeneic MSC therapy in preclinical and clinical studies. Also, the potential benefits of MSC technology are compelling and worthy of pursuit in accordance with the appropriate ethical standards and regulatory guidelines. Both basic and clinical research suggest that allogeneic MSCs are likely to solve many unmet clinical needs, and this can be made available as an off-the-shelf product. the injective if this study was to evaluate the efficacy of peri-ulcer administration of Umbilical cord MSC in the healing of DFU and assess the safety of peri-ulcer administration of Umbilical cord MSC in DFU by assess the • Proportion of patients with complete healing/closure of the target ulcer at any time during the 6-weeks period and proportion of patients with sustained complete closure for additional 6-weeks of follow-up. besides that, this study also will assess the time to complete closure of target ulcer and rate of reduction in the size of the target ulcer during the 6 weeks of follow-up and proportion of patients with at least 50% closure of target ulcer during the 6-weeks period. this study is Double-blind, placebo-controlled, randomized trial. Estimated duration for the main protocol (e.g., from starts of screening to last subject processed and end of the study) is approximately 9 months at Hospital Canselor Tunku Muhriz (HCTM), Jalan Yaacob Latif, Bandar Tun Razak, 56000 Kuala Lumpur, Wilayah Persekutuan, Malaysia using Ex-vivo cultured allogeneic mesenchymal stem cells (MSCs) supplied in vials consisting of 3 million cells, suspended in 1.5 ml saline (3 million cells/1.5 mL) with dosage of 1 million cells/cm2 of ulcer. The administration of the product will be through the peri-ulcer route. The injection will be done using a 24G needle and 1 ml/3 ml syringe approximately within 0.75 cm from the edge of the ulcer. The needle should enter the base of the ulcer from the edge.

Injection of Umbilical cord MSC (1 million cells/cm2 of the ulcer) will be administered at multiple sites (maximum of 30 sites) with intervals of 3 cm x 3 cm around the ulcer in a total volume of 0.1 to 0.2 ml per injection.

• Study Type: Interventional
• Enrollment (Estimated): 22
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Abid Nordin; Phone Number: +6012-712 2468; Email: abid@medcentral.com.my

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients between 18-70 years old.
• Patients have type 2 diabetes mellitus
• Patients with HbA1c, less than or equal to 10%.
• Patients who were presented with an ulcer size between 8 to 12 cm2, have been diagnosed as full-thickness DFU.
• Adequate vascular perfusion (ABI ≥ 0.7 and < 1.3)
• Patients who are able and willing to provide consent and agree to comply with study procedures and follow-up evaluations.

Exclusion Criteria:

• Patients who are not diabetic.
• Patients with 2 or more ulcers.
• Patients with a history of participating in another stem cells trial or therapy within 3 months.
• Patients who are unsuitable to participate the clinical trial as determined by Investigators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Allogeneic mesenchymal stem cells (MSCs); Peri-ulcer injection of Umbilical cord MSC (1.0 million cells/cm2 of the ulcer) will be administered at multiple sites (maximum of 30 sites) with intervals of 3 cm x 3 cm around the ulcer with total volume of 0.1 to 0.2 ml per injection. Whatever IMP is drawn into the syringe for administration to the wound must be completely dispensed and nothing should be left in the syringe. Number of injections and volume of each injection can be as per Investigator's discretion. The same to be recorded in the source notes and CRF.The injection will be done approximately using a 24G needle and 1 ml/3ml syringe approximately within 0.75 cm from the edge of the ulcer. The needle should enter the base of the ulcer from the edge. After injection, patients must be in a lying down position for at least one hour in daycare center at the site and monitoring of oxygen saturation will be done up to 2 hours ± 10 minutes after the administration of the product.	Drug: Allogeneic mesenchymal stem cells (MSCs); Dosage · Dosing of IMP is based on ulcer size. The recommended dose is 1 million cells/cm2 of ulcer. Administration · Injections will be done through peri-ulcer route. · Injection will be done 0.75 cm from the edge of the ulcer. · Injection will be done using 24G. The volume of injection will 4.0 - 6.0 ml per patient (maximum 0.1 to 0.2 ml per injection; 30 injections maximum per patients); Other Names: Ex-vivo cultured allogeneic mesenchymal stem cells (MSCs) supplied in vials consisting of 3 million cells, suspended in 1.5 ml saline.
Placebo Comparator: Normal Saline; The blinded placebo group will be injected with normal saline (NSand the volume to be injected is similar to the area of ulcer (2 mL of normal saline per 1 cm2 of ulcer). each injection will be o.1 to 0.2 ml normal saline (maximum injection will be 30 injection peri ulcer)	Drug: Normal Saline; Dosage · Dosing of placebo is based on ulcer size. the volume will be samed as the experimental groups which is 2 ml per 1cm2 Administration · Injections will be done through peri-ulcer route. · Injection will be done 0.75 cm from the edge of the ulcer. · Injection will be done using 24G. The volume of injection will 4.0 - 6.0 ml per patient (maximum 0.1 to 0.2 ml per injection; 30 injections maximum per patients); Other Names: Placebo (Normal Saline)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with complete healing/closure of the target ulcer at any time during the 6-weeks period.	ulcer assessment (area and photograph)	The monitoring of ulcer healing progress will continue until week 6 after the administration of the investigational medicinal product (IMP). The primary measure of effectiveness will be evaluated during the 8th visit which will take place at week 6.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of patients with sustained complete closure for additional 6-weeks of follow-up.	ulcer assessment (area and photograph)	weekly follow up 4 times, followed by biweekly followed up two times and one monthly follow up (weeks 12)
Time to complete closure of target ulcer.	ulcer assessment (area and photograph)	weekly follow up 4 times, followed by biweekly followed up two times and one monthly follow up (weeks 12)
Rate of reduction in the size of the target ulcer during the 6 weeks of follow-up.	ulcer assessment (area and photograph)	weekly follow up 4 times, followed by biweekly followed up two times and one monthly follow up (weeks 12)
The proportion of patients with at least 50% closure of target ulcer during the 6-weeks period	ulcer assessment (area and photograph)	weekly follow up 4 times, followed by biweekly followed up two times and one monthly follow up (weeks 12)

Collaborators and Investigators

• Sponsor: Supergenics Life Science Sdn. Bhd.
• Investigators: Principal Investigator: Mohd Yazid Bajuri, Hospital Canselor Tunku Muhriz (HCTM)

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: January 21, 2024
• First Submitted That Met QC Criteria: January 21, 2024
• First Posted (Actual): January 30, 2024

Study Record Updates

• Last Update Posted (Actual): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Stem cells; DFU; Per-ulcer
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Endocrine System Diseases; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Foot Diseases; Diabetic Foot; Foot Ulcer; Ulcer
• Other Study ID Numbers: SGT-DFU-23-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No