The Immunostimulatory Effects of Gentamicin

NCT05303909 | Terminated Phase 2

• 1 other identifier: GENT-YF-01B
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

Gentamicin is one of the few aminoglycoside antibiotics which are approved for parenteral use in Singapore. As with other aminoglycosides, gentamicin is primarily bactericidal against Gram-negative organisms. It is well known that viral infection increases susceptibility to bacterial infection; increased rates of Gram-negative bacterial sepsis due to gastrointestinal tract bacterial translocation have been reported in Ebola and dengue patients. Gentamicin use in viral infection could thus improve clinical outcome by inhibiting both viral and opportunistic Gram-negative bacterial infection. Parenteral aminoglycosides do not cause perturbations or dysbiosis within the human gut microbiome. This is of importance as dysbiosis would not only increase the risk of antibiotic-resistant bacteria selection within the intestinal tract, it could also lead to negative downstream effects on the host response to infection by altering activation states of both innate and adaptive immunity. Thus, parenteral gentamicin may offer a unique approach to preventing both viral and downstream secondary Gram-negative bacterial infection, while at the same time minimizing the potential development of antibiotic resistance. The overarching goal of this study is to demonstrate that parenteral aminoglycosides exert broad-spectrum antiviral effects against RNA viruses in humans through their immunostimulatory properties. Using the live attenuated yellow fever (YF17D; stamaril) vaccine as an experimental viral infection model, a placebo controlled clinical trial will be carried out to demonstrate the efficacy of parenteral gentamicin in preventing viremia.

Conditions

Healthy Volunteers

Keywords

Gentamicin; viremia; YF17D

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects with detectable YF17D viremia

  The proportion of subjects with detectable YF17D viremia after YF17D vaccination

  14 days

Secondary Outcomes (6)

• Peak YF17D viremia levels

  14 days

• Duration of detectable YF17D viremia

  14 days

• Neutralising antibody titers against YF17D

  30 days

• Rates of symptomatic infection after YF17D vaccination

  30 days

• Levels of innate immune gene expression

  6 days

Other Outcomes (1)

• Cellular immune response

  Day 30

Study Arms (2)

Gentamicin

EXPERIMENTAL

a single dose of IV gentamicin at a dose of 5 mg/kg (rounded up to the nearest 10mg) diluted in 100mls of 0.9% normal saline infused over 30 minutes via a peripheral vein

Drug: Gentamicin

Placebo

PLACEBO COMPARATOR

100mls of 0.9% normal saline as placebo infused over 30 minutes via a peripheral vein

Drug: Placebo

Interventions

Gentamicin DRUG

a single dose of IV gentamicin at a dose of 5 mg/kg infused over 30 minutes via a peripheral vein. Followed by administration of YF17D vaccine (stamaril) 0.5mls via subcutaneous injection into the deltoid region of the right or left arm.

Gentamicin

Placebo DRUG

100mls of 0.9% normal saline as placebo infused over 30 minutes via a peripheral vein. Followed by administration of YF17D vaccine (stamaril) 0.5mls via subcutaneous injection into the deltoid region of the right or left arm.

Placebo

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adults, 21-50 years of age at time of screening
• Satisfactory baseline medical assessment as assessed by physical examination and a stable health status. The laboratory values must be within the normal range of the assessing site or show abnormalities that are deemed not clinically significant as judged by the investigator. A stable health status is defined as the absence of a health event satisfying the definition of a serious adverse event.
• Accessible vein for blood collection.
• Subjects who are willing to comply with the requirements of the study protocol and scheduled visits. (e.g. return for follow-up visits) and who are willing to make themselves available for the duration of the study, with access to a consistent means of telephone contact, which may be either at home or at the workplace, land line, or mobile, but NOT a pay phone or other multiple-user device (i.e. a common-use phone serving multiple rooms or apartments).
• Ability to provide informed consent
• Female subjects of non-child bearing potential due to surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause. Post-menopausal subjects must have had at least 12 months of natural (spontaneous) amenorrhea.
• Female subjects of childbearing potential with negative urine pregnancy tests on the day of screening and day of antibiotic administration.
• Both male (if he has a partner of childbearing potential) and female subjects (of childbearing potential) must agree to use adequate and reliable contraceptive measures (e.g. spermicides, condoms, contraceptive pills) or practice abstinence for 10 days after vaccination

You may not qualify if:

• History of presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, neuropsychiatric, haematological, endocrine or immunosuppressive disorders that would be a risk factor when administered gentamicin or YF17D vaccine.
• Previous receipt of YF17D vaccine (stamaril) or any other yellow fever vaccines.
• Previous history of Yellow fever virus infection
• Known allergy to YF17D vaccine (stamaril) or its components
• Known allergy to gentamicin
• History of severe food/drug/vaccine allergies e.g. angioedema, anaphylaxis
• Known allergy to egg or egg products
• History of thymus gland disease
• Diagnosed with cancer or on treatment for cancer (with the exception of localized basal cell carcinoma) within 3 years prior to screening
• Diagnosed with neuromuscular disorders
• Evidence of clinically significant anemia (Hb \<10 g/dl)
• Blood donation exceeding \>450mls in the past 3 months
• Presence of acute infection in the preceding 7 days or presence of a temperature ≥ 38.0°C (oral or tympanic temperature assessment), or acute symptoms greater than of "mild" severity on the scheduled date of first dose
• Woman who is pregnant or breast feeding
• Evidence of substance abuse, or previous substance abuse including alcohol

Sponsors & Collaborators

• Singapore General Hospital: lead

Study Sites (1)

Singapore General Hospital

Singapore, 169074, Singapore

Location

MeSH Terms

Conditions

Viremia

Interventions

Gentamicins

Condition Hierarchy (Ancestors)

Virus Diseases; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aminoglycosides; Glycosides; Carbohydrates

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This is a double blind placebo controlled trial
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Subjects will be randomized in a 1:1 ratio to receive either a single dose of IV gentamicin at dose of 5 mg/kg or 0.9% normal saline placebo on Day 0 in a double-blind fashion, followed by YF17D vaccination 30 minutes later.

Study Record Dates

• First Submitted: March 13, 2022
• First Posted: March 31, 2022
• Study Start: May 11, 2022
• Primary Completion: May 13, 2024
• Study Completion: May 13, 2024
• Last Updated: May 16, 2024

Record last verified: 2024-05

Locations

SG (1)