Stimulan-VG + Antibiotics for Diabetic Foot Infection

(BLADE-VG2 Trial)

Not currently recruiting at 10 trial locations

Overseen By Daniel Roberts, In-House CRA MCRA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Biocomposites Ltd

Must not be taking: Corticosteroids, Glycopeptides, Aminoglycosides

Disqualifiers: Charcot foot, Severe infection, Renal impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 4-6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Stimulan-VG, a product mixed with the antibiotics vancomycin and gentamicin, combined with antibiotics for individuals with diabetic foot infections that have reached the bone. The goal is to assess the safety and effectiveness of this new approach compared to the standard treatment, which typically involves only antibiotics. Individuals with diabetes and a foot infection affecting the bones, particularly those requiring surgery to clean the infected area, might be suitable candidates for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are taking high-dose corticosteroids or have allergies to certain antibiotics, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that Stimulan-VG, a treatment using calcium sulfate granules, has potential in treating infections. In earlier studies, these granules improved outcomes for patients with diabetic foot ulcers and bone infections related to diabetes, suggesting the treatment might be safe and well-tolerated.

Moreover, some countries have already approved Stimulan for use with certain antibiotics to treat bone and soft tissue infections, indicating a good safety record, although results can vary.

While this trial is in its early stages, with much still to learn about its safety, the findings so far offer some reassurance. Participants in this study can help further confirm the safety and effectiveness of Stimulan-VG for treating diabetic foot infections. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for diabetic foot infections rely on systemic antibiotics administered over several weeks. However, Stimulan-VG is unique because it delivers antibiotics directly to the infection site through a dissolvable calcium sulfate bead. This local delivery method not only targets bacteria more precisely but may also reduce the duration and side effects associated with prolonged antibiotic use. Researchers are excited about Stimulan-VG because it could potentially lead to faster healing and fewer complications compared to standard treatments.

What evidence suggests that Stimulan-VG and antibiotics could be effective for diabetic foot infection?

Research shows that Stimulan-VG, a special material mixed with antibiotics, could help treat diabetic foot bone infections. In this trial, one group of participants will receive Stimulan-VG after surgical debridement, along with systemic antibiotics for a short duration. Studies have found that this treatment delivers antibiotics directly to the infected area, reducing the risk of complications. Previous research suggests that these antibiotic-filled granules can combat infections in diabetic foot wounds and bone infections. The treatment works by slowly releasing antibiotics at the infection site, aiding in more effective clearance. This new approach makes Stimulan-VG a potentially effective option for managing diabetic foot infections. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

Adults with diabetic foot osteomyelitis of the forefoot who need surgical debridement but not amputation. They must have diabetes, a confirmed diagnosis of DFO, and agree to contraceptive guidance if applicable. Excluded are those with muscular disorders, severe immune suppression or recent high-dose steroids use, active substance abuse, very high HbA1c levels (>12%), severe kidney issues, large ulcers (>3.5 cm), allergies to trial drugs, significant arterial disease or certain infections.

Inclusion Criteria

I am not pregnant, not breastfeeding, and follow specific birth control measures.

I need surgery to remove damaged tissue or amputation of a toe due to an infection that has spread.

I am either male or female.

Exclusion Criteria

I had a limb amputated less than 30 days ago.

I have a history of muscle disorders like myasthenia gravis or Parkinson's.

I have a bone infection not in my forefoot.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo surgical debridement and receive either STIMULAN VG with an abbreviated course of systemic antibiotics (3 days ±2 days) or a full course (4-6 weeks) of systemic antibiotics

4-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments for ulcer healing and absence of osteomyelitis

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Stimulan-VG
• Systemic Antibiotics

Trial Overview The trial is testing Stimulan-VG plus standard systemic antibiotics against just the standard care for treating diabetic foot osteomyelitis in the forefoot. It aims to assess safety and measure how much better one group does compared to the other.

How Is the Trial Designed?

Group I: STIMULAN VG Experimental Treatment 2 Interventions

Participants will receive STIMULAN VG on Day 1 following surgical debridement. Systemic antibiotics for 3 days ± 2 days following the debridement surgery.

Group II: Standard of Care Active Control 1 Intervention

Participants will receive Systemic antibiotics for 4-6 weeks following the debridement surgery.

Stimulan-VG is already approved in United States, European Union, Canada for the following indications:

Approved in United States as STIMULAN VG for:

• Diabetic foot osteomyelitis
• Stage IV pressure ulcers

Approved in European Union as STIMULAN for:

• Wound healing
• Bacterial infection
• Carrying antibiotics in bone and soft tissue

Approved in Canada as STIMULAN for:

• Bacterial infection

Who Is Running the Clinical Trial?

Biocomposites Ltd

Lead Sponsor

Trials

6

Recruited

270+

MCRA

Industry Sponsor

Trials

40

Recruited

11,100+

Parexel

Industry Sponsor

Trials

322

Recruited

137,000+

Peyton Howell

Parexel

Chief Executive Officer

Master of Healthcare Administration from The Ohio State University, Bachelor of Arts in Health Communications from the University of Illinois

Dr. Austin Smith

Parexel

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Published Research Related to This Trial

Diabetes induced by streptozotocin in rats did not significantly alter their sensitivity to the behavioral effects of amphetamine and other drugs, despite changes in locomotion and body weight.

While baseline locomotion was lower in diabetic rats, amphetamine still effectively increased locomotion in both diabetic and control rats, indicating that the drug's efficacy remains intact even in the context of diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Behavioral effects of amphetamine in streptozotocin-treated rats. Sevak, RJ., Koek, W., Daws, LC., et al.[2019]

Fenoldopam, a selective dopamine-1 agonist, effectively stimulates cyclic AMP (cAMP) production in renal cells, indicating its potential role in promoting natriuresis and diuresis through DA1 receptor activation.

Although fenoldopam is more potent than dopamine in stimulating cAMP synthesis, it has lower maximum efficacy, acting as a partial agonist and competitive antagonist at DA1 receptors, which may influence its therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fenoldopam is a partial agonist at dopamine-1 (DA1) receptors in LLC-PK1 cells. Grenader, A., Healy, DP.[2013]

In diabetic rats with low insulin levels, nicotine did not increase dopamine levels in the nucleus accumbens, likely due to increased GABA and decreased glutamate levels, indicating a disruption in the neurochemical response to nicotine.

Insulin supplementation in these diabetic rats restored the neurochemical effects of nicotine, normalizing dopamine and acetylcholine levels in the mesolimbic pathway, suggesting that insulin plays a crucial role in modulating nicotine's effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin restores the neurochemical effects of nicotine in the mesolimbic pathway of diabetic rats. Cruz, B., Carcoba, LM., Flores, RJ., et al.[2023]

Fenoldopam, a selective DA1 agonist, significantly increases cyclic AMP levels in the trabecular meshwork of porcine and canine eyes, indicating its potential role in regulating intraocular pressure.

The increase in cyclic AMP levels is specifically mediated through DA1 receptors, as shown by the 90% inhibition of this effect when a DA1 receptor antagonist was used, confirming the presence of these receptors in the trabecular meshwork.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of dopamine receptor activation on the level of cyclic AMP in the trabecular meshwork. Karnezis, TA., Tripathi, BJ., Dawson, G., et al.[2013]

In a study involving freely moving streptozotocin (STZ)-diabetic male rats, it was found that both basal levels of dopamine and the increase in dopamine induced by amphetamine were significantly lower compared to normal rats, indicating impaired dopamine function in diabetes.

The findings suggest that diabetes may lead to decreased activity of dopamine neurons and increased sensitivity of dopamine receptors in the mesolimbic system, which could have implications for understanding mood and reward processing in diabetic conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diabetes decreases limbic extracellular dopamine in rats. Murzi, E., Contreras, Q., Teneud, L., et al.[2019]

Vancomycin is an important antibiotic for treating severe infections caused by Gram-positive bacteria, especially in cases of MRSA and for patients allergic to penicillins, but its use can lead to significant adverse effects such as nephrotoxicity and red man syndrome.

Improper dosing and prolonged use of vancomycin can increase the risk of treatment failures and toxicity, highlighting the need for further studies to optimize its administration and ensure safe and effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of vancomycin with its therapeutic and adverse effects: a review. Bruniera, FR., Ferreira, FM., Saviolli, LR., et al.[2022]

Vancomycin is a highly effective antibiotic specifically targeting gram-positive bacteria, particularly useful for treating methicillin-resistant staphylococcal infections and gram-positive endocarditis, with a low risk of developing bacterial resistance due to its multiple modes of action.

While 'red neck syndrome' is a common side effect associated with rapid intravenous infusion, the overall toxicity of vancomycin is less significant than previously believed, and serious side effects like nephrotoxicity and ototoxicity are rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vancomycin: an update. Cheung, RP., DiPiro, JT.[2019]

Vancomycin is an effective antibiotic for serious staphylococcal infections, especially when patients cannot use penicillins or cephalosporins, and is typically administered intravenously at a dose of 1 g every 12 hours for those with normal kidney function.

It is generally safe with low toxicity, primarily neurotoxicity, which is rare if serum levels remain at or below 30 micrograms/ml.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vancomycin. Geraci, JE.[2013]

A 57-year-old male experienced unusually high serum levels of vancomycin (39 μg/ml) during treatment for Clostridium difficile colitis, leading to neurological symptoms and sexual dysfunction.

Discontinuing oral vancomycin and using hemodialysis effectively reduced serum levels to 26 μg/ml and resulted in a rapid resolution of symptoms, highlighting the risk of vancomycin accumulation in patients with intestinal disease and reduced renal function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Uncommon Case of Oral Vancomycin Neurotoxicity With Sexual Dysfunction. Almohammadi, A., Shahada, O., Almadani, AZ., et al.[2021]

Pharmacokinetic drug-drug interactions (DDIs) between antiseizure medications (ASMs) and anti-infectives in children can significantly affect the efficacy and safety of treatments, with valproate (VPA) levels dropping by about 60% when combined with carbapenem antibiotics, leading to seizure recurrence.

Voriconazole, an antifungal, interacts with several ASMs, causing bidirectional DDIs that can either increase ASM levels or reduce voriconazole efficacy, highlighting the need for careful monitoring and management of these interactions in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of pharmacokinetic drug interactions between antimicrobial and antiseizure medications in children. Zaccara, G., Lattanzi, S.[2021]

Citations

1. biocomposites.com biocomposites.com/news/biocomposites-announces-two-new-phase-ii-clinical-trials-of-stimulan-vg-a-calcium-matrix-antibiotic-carrier-mixed-with-vancomycin-and-gentamicin-in-the-u-s/

Biocomposites Announces Two New Phase II Clinical Trials Biocomposites is now recruiting patients to its BLADE-VG2 trial, which will evaluate the safety and efficacy of STIMULAN VG in treating diabetic foot ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11964986/

Efficacy and safety of a bio‐absorbable antibiotic delivery ... Calcium sulphate granules (Stimulan Rapid Cure™) were shown to reduce adverse outcomes both in patients with infected DFU and DFO in non‐ ...

3. biocomposites.com biocomposites.com/news/biocomposites-to-present-data-on-stimulan-and-genex-at-eccmid-2022/

Biocomposites Presents Data At ECCMID 2022 | International Research findings from two studies demonstrate the antimicrobial effectiveness of STIMULAN® and genex®, when mixed with antibiotics.

4. clinicaltrialsarena.com clinicaltrialsarena.com/news/biocomposites-initiates-two-phase-ii-trials-of-stimulan-vg-in-us/

Biocomposites initiates two-Phase II trials of STIMULAN VG ... The two trials, BLADE-VG2 and BLADE-OPU2, will evaluate the safety and efficacy of STIMULAN VG to treat patients with diabetic foot osteomyelitis, and stage IV ...

5. journals.asm.org journals.asm.org/doi/10.1128/aac.02012-20

Efficacy of Topical Vancomycin- and Gentamicin-Loaded ... These data support further studies of the topical release of antibiotics from calcium sulfate beads in diabetic foot infections.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10332169/

The use of Stimulan in bone and joint infections Our multicentre experience confirmed that surgical debridement along with calcium sulphate bead insertion was effective in treating bone and joint infections.

7. biocomposites.com biocomposites.com/our-products/stimulan/

STIMULAN® Rapid Cure Beads | Bone & Joint Infection In the EU, UK and Saudi Arabia, STIMULAN is approved for mixing with vancomycin, gentamicin and tobramycin for use in bone and soft tissue.