Stimulan-VG + Antibiotics for Diabetic Foot Infection

(BLADE-VG2 Trial)

Recruiting in Palo Alto (17 mi)

+8 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Biocomposites Ltd

Must not be taking: Corticosteroids, Glycopeptides, Aminoglycosides

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

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment called STIMULAN VG for patients with serious foot infections due to diabetes. The treatment involves placing a special material in the infected area during surgery and using antibiotics for a limited time. The goal is to see if this method is safe and effective compared to the usual antibiotic treatment.

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 the combination of Stimulan-VG and antibiotics safe for humans?

Vancomycin, one of the antibiotics in this treatment, is generally safe but can cause side effects like 'red neck syndrome' (redness and itching on the neck and back) if given too quickly, and rare cases of kidney and ear problems. It's important to monitor its levels in the body, especially in people with kidney issues, to avoid these side effects. ^{1 2 3 4 5}

What makes the Stimulan-VG + Antibiotics treatment unique for diabetic foot infections?

Stimulan-VG + Antibiotics is unique because it combines a local antibiotic delivery system with systemic antibiotics, potentially enhancing infection control directly at the site while also treating the body as a whole. This dual approach may offer more effective management of diabetic foot infections compared to standard systemic antibiotic treatments alone. ^{6 7 8 9 10}

Research Team

Eligibility Criteria

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 am 18 years old or older.

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

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.

Trial Timeline

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

Treatment Details

Interventions

• Stimulan-VG (Bone Graft Substitute)
• Systemic Antibiotics (Antibiotic)

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.

Participant Groups

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 Canada for the following indications:

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

Findings from Research

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]

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]

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]

References

1. Italy pubmed.ncbi.nlm.nih.gov

The use of vancomycin with its therapeutic and adverse effects: a review. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Vancomycin: an update. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Vancomycin. [2013]

4. United States pubmed.ncbi.nlm.nih.gov

Uncommon Case of Oral Vancomycin Neurotoxicity With Sexual Dysfunction. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

A review of pharmacokinetic drug interactions between antimicrobial and antiseizure medications in children. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Behavioral effects of amphetamine in streptozotocin-treated rats. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

Insulin restores the neurochemical effects of nicotine in the mesolimbic pathway of diabetic rats. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Effects of dopamine receptor activation on the level of cyclic AMP in the trabecular meshwork. [2013]

10. Ireland pubmed.ncbi.nlm.nih.gov

Diabetes decreases limbic extracellular dopamine in rats. [2019]