Vancomycin for Obesity

Overseen By Amit Pai, PharmD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Michigan

Must not be taking: GLP1 agonists, Ototoxic drugs

Disqualifiers: Pregnancy, Allergies, Cardiovascular, Renal, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dosing method for the antibiotic vancomycin in obese adults by testing two approaches: dosing based on weight and dosing based on kidney function. Researchers seek to identify which method yields better results and assess any safety concerns. Participants will be divided into two groups to receive a single dose of vancomycin, either according to their weight or kidney function. The trial seeks healthy obese adults who weigh at least 80 kg (about 176 pounds) and have normal kidney function. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants an opportunity to contribute to foundational knowledge.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it excludes participants taking ototoxic drugs (medications that can damage hearing). It's best to discuss your current medications with the trial team.

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

Research shows that dosing vancomycin presents challenges in obese patients. Studies have found that these patients often exhibit higher initial drug levels in their blood, increasing the risk of excessive drug presence. Without early intervention, this can lead to harmful side effects, so careful monitoring is crucial.

Vancomycin treats infections but requires special attention in obese patients. Obesity affects how the drug functions in the body, complicating the achievement of safe and effective levels. Current guidelines recommend dosing based on lean body weight (weight without fat) and regularly checking blood levels to ensure safety.

In summary, while vancomycin is a common treatment, safely dosing it in obese patients requires careful management to prevent side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Vancomycin is being explored for obesity treatment with a unique approach. Unlike typical obesity treatments that often focus on dietary changes, exercise, or medications like orlistat and liraglutide, vancomycin is an antibiotic. Researchers are interested in its potential because it uses kidney function stratified dosing, which is different from the weight-stratified dosing common in current care. This method could optimize dosing efficiency and reduce side effects, offering a fresh angle in tackling obesity.

What evidence suggests that vancomycin might be an effective treatment for obesity?

Research has shown that determining the right dose of vancomycin for obese patients can be challenging. Some studies suggest that using total body weight to decide the dose might lead to excessive amounts, potentially causing harm. Vancomycin can accumulate in the body, increasing the risk of kidney damage, particularly in obese individuals. In this trial, one group will receive weight-stratified dosing as the current standard of care. Another group will receive kidney function-stratified dosing, which evidence suggests might be more effective and safer, as it considers how well the kidneys eliminate the drug. Other research indicates that obesity doesn't significantly affect how vancomycin levels stabilize in the body, so dosing should consider more than just body weight. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for obese adults who need vancomycin treatment. Participants must be willing to provide blood and urine samples, undergo body composition measurements, and attend clinic visits for exams and tests.

Inclusion Criteria

I am obese, with a BMI in one of the specified ranges.

I weigh 80 kg or more.

My kidney function, measured by creatinine clearance, is within the required range.

Exclusion Criteria

History of severe allergic diseases including drug allergies, with the exception of seasonal allergies

Participants with underlying hearing loss

Pregnant or lactating females

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of vancomycin based on either their weight or kidney function, with blood and urine samples collected for pharmacokinetic analysis

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including body composition measurements and laboratory evaluations

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Vancomycin

Trial Overview The study is testing how best to dose vancomycin in obese individuals by comparing two methods: one based on the patient's weight and the other on kidney function. It aims to determine which method provides better drug exposure.

How Is the Trial Designed?

Group I: Test Experimental Treatment 1 Intervention

Kidney function stratified dosing

Group II: Control Active Control 1 Intervention

Weight-stratified dosing as the current standard of care

Vancomycin is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Vancocin for:

• Severe infections caused by susceptible strains of methicillin-resistant staphylococci
• Enterocolitis caused by Staphylococcus aureus
• Staphylococcal endocarditis

Approved in European Union as Vancomycin for:

• Severe infections caused by Gram-positive bacteria
• Endocarditis
• Peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD)

Approved in Canada as Vancomycin for:

• Severe infections caused by susceptible strains of methicillin-resistant staphylococci
• Enterocolitis caused by Staphylococcus aureus

Approved in Japan as Vancomycin for:

• Severe infections caused by Gram-positive bacteria
• Endocarditis

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

Published Research Related to This Trial

Obesity is linked to serious health risks, including coronary heart disease and premature death, independent of traditional risk factors, highlighting the need for comprehensive evaluation and treatment strategies.

Effective treatment for obesity should focus on moderate caloric reduction, improved eating habits, and increased physical activity, with group therapy showing promising results; very hypocaloric diets can also improve mood and reduce sleep needs in severely obese patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Evaluation and treatment of obesity in clinical practice]. Keller, U., van der Werf, H., Stohler, R.[2012]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9578159/

Evaluation of Vancomycin Accumulation in Patients With Obesity Vancomycin accumulation may place obese patients at increased risk for nephrotoxicity, which has been demonstrated in previous studies [7–9]. In a single-center ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1341321X25002351

Development and External Validation of a Population ... Our model shows that determining effective vancomycin doses for overweight and obese patients depend on estimated CCr rates, AdjBW, BUN levels, ...

3. mdpi.com mdpi.com/2079-6382/14/9/895

Impact of Obesity on Serum Concentrations of Vancomycin ... According to our results, obesity does not significantly influence the achievement of targeted steady-state vancomycin concentrations. A possible explanation ...

4. academic.oup.com academic.oup.com/jac/article/73/11/3081/5091849

Dosing vancomycin in the super obese: less is more Current guidance recommends dosing using total body weight (TBW) irrespective of BMI, which leads to the calculation of large, potentially toxic doses in obese ...

5. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.965284/full

Dose optimization of vancomycin in obese patients Our study supports the practice of administering loading dose (20–25 mg/kg) followed by maintenance dose (15–25 mg/kg) of vancomycin in obese ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10081578/

Dose optimization of vancomycin in obese patients Dose based on Age: Initial trough concentration of vancomycin above 20 μg/mL occurred more often in overweight and obese patients. Special ...

7. accpjournals.onlinelibrary.wiley.com accpjournals.onlinelibrary.wiley.com/doi/10.1002/phar.4613

Impacts of age and BMI on vancomycin model choice in a ... Without early intervention, obese patients are at risk for drug toxicity due to overexposure to vancomycin.

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1341321X15000720

The association of elevated trough serum vancomycin ... Obese patients display differences in vancomycin drug disposition, which may complicate attainment of appropriate serum vancomycin concentrations (SVCs).

9. med.stanford.edu med.stanford.edu/content/dam/sm/bugsanddrugs/documents/antimicrobial-dosing-protocols/SHC-ABX-Obesity-Dosing-Guide.pdf

SHC-ABX-Obesity-Dosing-Guide.pdf Obesity: ATS/CDC Guidelines recommend dosing based on estimated lean body weight, though data in obese is poor; TDM is recommended.