Healthy VolunteersPhase 2NCT05303909
The Immunostimulatory Effects of Gentamicin
A Phase 2 study testing Gentamicin in people with Healthy Volunteers, run by Singapore General Hospital at 1 site in Singapore.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Gentamicin
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 33 participants
- Where
- 1 siteSingapore
- Study dates
- 11 May 2022to 13 May 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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
- Participation in a study involving administration of an investigational compound (including investigational vaccines) within the past three months, or planned participation during the duration of this study.
- Receipt of anti-inflammatory drugs (such as NSAIDs or steroids) in the past 7 days before the first study drug/vaccine dose.
- Receipt of any licensed vaccine in the past 30 days before the first study drug/vaccine dose.
- Any condition that, in the opinion of the investigator, would complicate or compromise the study or wellbeing of the subject.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Immunostimulatory Effects of Gentamicin: Translating Aminoglycoside Antibiotics Into Antiviral Therapeutics for Pandemic Response (Part B)
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.
Read the detailed description
Informed written consent will be sought from subjects who fulfil criteria for enrolment. All consented subjects will undergo screening, which includes physical examination, full blood count, liver function test, serum creatinine, and urinary pregnancy test (for female subjects of child-bearing potential).
All eligible subjects will proceed to Day 0, where they will undergo randomization to receive either IV gentamicin at a dose of 5 mg/kg or 0.9% normal saline placebo, followed by YF17D vaccination 30 minutes later i.e. 30 minutes after completion of gentamicin/placebo infusion. Urine pregnancy test (for female subjects of child-bearing potential) will be performed prior to study drug administration. Baseline physical examination and vital signs will be done as well. On Day 0, research blood sampling will be performed prior to gentamicin/placebo administration.
Subsequently, study subjects will return for follow-up visits on D1, D4, D6, D14 and D30. Research blood samples will be taken at each visit. Physical examination, vital signs, and review of adverse events will be done at each of the visit as well.
At any time post-study drug or YF17D administration, subjects will be trained to observe for systemic AEs. A diary will also be given to the subjects to record such events should they occur during this period. Should they develop systemic symptoms that require intervention, they will report to the study site for medical evaluation and receive the appropriate therapy. Duration of symptoms will be recorded. Any concomitant medication use during this period will also be recorded.
During the study, full history taking and physical examination will be performed at both scheduled and unscheduled visits. The Common Terminology Criteria for Adverse Events (CTCAE), routinely employed in clinical trials, will be used to define AE terminology and severity. Management of AEs is at the discretion of the study team PI and co-Is, guided by severity and clinical indication for intervention. All medication prescribed for the management of AEs will be documented in the medication/concomitant medication clinical record form.
- Conditions
- Healthy Volunteers
- Being tested
- Gentamicin, Placebo
- Keywords
- Gentamicin, viremia, YF17D
- Medical subject headings
- Viremia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GentamicinDrug
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Gentamicin |
| Placebo | Placebo comparator | 100mls of 0.9% normal saline as placebo infused over 30 minutes via a peripheral vein Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of subjects with detectable YF17D viremia
The proportion of subjects with detectable YF17D viremia after YF17D vaccination
Measured: 14 days
Secondary outcomes (6)
Peak YF17D viremia levels
Peak YF17D viremia levels after YF17D vaccination
Measured: 14 days
Duration of detectable YF17D viremia
Duration (in days) of detectable YF17D viremia after YF17D vaccination
Measured: 14 days
Neutralising antibody titers against YF17D
Neutralising antibody titers at study Day 30 against YF17D after YF17D vaccination
Measured: 30 days
Rates of symptomatic infection after YF17D vaccination
Rates of symptomatic infection after YF17D vaccination
Measured: 30 days
Levels of innate immune gene expression
Levels of innate immune gene expression in subjects.
Measured: 6 days
Mean YF17D viremia levels
Mean YF17D viremia levels after YF17D vaccination
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2022
- Study start11 May 2022
- Primary completion13 May 2024
- Study completion13 May 2024
Why it stopped: slow recruitment due to COVID19
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by Singapore General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Singapore General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05303909
- Sponsor's protocol ID
- GENT-YF-01B
- Status last verified
- May 2024
- First submitted
- 13 Mar 2022
- Last updated
- 16 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Immunostimulatory Effects of Gentamicin: Translating Aminoglycoside Antibiotics Into Antiviral Therapeutics for Pandemic Response (Part B)
- ClinicalTrials.gov ID
- NCT05303909
- Acronym / sponsor ID
- GENT-YF-01B
- Conditions
- Healthy Volunteers
- Keywords
- Gentamicin, viremia, YF17D
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: slow recruitment due to COVID19
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Singapore General HospitalUniversity, hospital or other
- Study start
- 11 May 2022 (actual)
- Primary completion
- 13 May 2024 (actual)
- Study completion
- 13 May 2024 (actual)
- First posted
- 31 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Informed written consent will be sought from subjects who fulfil criteria for enrolment. All consented subjects will undergo screening, which includes physical examination, full blood count, liver function test, serum creatinine, and urinary pregnancy test (for female subjects of child-bearing potential).
All eligible subjects will proceed to Day 0, where they will undergo randomization to receive either IV gentamicin at a dose of 5 mg/kg or 0.9% normal saline placebo, followed by YF17D vaccination 30 minutes later i.e. 30 minutes after completion of gentamicin/placebo infusion. Urine pregnancy test (for female subjects of child-bearing potential) will be performed prior to study drug administration. Baseline physical examination and vital signs will be done as well. On Day 0, research blood sampling will be performed prior to gentamicin/placebo administration.
Subsequently, study subjects will return for follow-up visits on D1, D4, D6, D14 and D30. Research blood samples will be taken at each visit. Physical examination, vital signs, and review of adverse events will be done at each of the visit as well.
At any time post-study drug or YF17D administration, subjects will be trained to observe for systemic AEs. A diary will also be given to the subjects to record such events should they occur during this period. Should they develop systemic symptoms that require intervention, they will report to the study site for medical evaluation and receive the appropriate therapy. Duration of symptoms will be recorded. Any concomitant medication use during this period will also be recorded.
During the study, full history taking and physical examination will be performed at both scheduled and unscheduled visits. The Common Terminology Criteria for Adverse Events (CTCAE), routinely employed in clinical trials, will be used to define AE terminology and severity. Management of AEs is at the discretion of the study team PI and co-Is, guided by severity and clinical indication for intervention. All medication prescribed for the management of AEs will be documented in the medication/concomitant medication clinical record form.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Gentamicin | Experimental | Drug: Gentamicina 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 |
| Placebo | Placebo comparator | Drug: Placebo100mls of 0.9% normal saline as placebo infused over 30 minutes via a peripheral vein |
Who may qualify
- Ages
- 21 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Gentamicina 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. | Drug | Gentamicin |
| Placebo100mls 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. | Drug | Placebo |
Primary outcome
Proportion of subjects with detectable YF17D viremia
Time frame: 14 days
The proportion of subjects with detectable YF17D viremia after YF17D vaccination
6 secondary outcomes
Peak YF17D viremia levels
Time frame: 14 days
Duration of detectable YF17D viremia
Time frame: 14 days
Neutralising antibody titers against YF17D
Time frame: 30 days
Rates of symptomatic infection after YF17D vaccination
Time frame: 30 days
Levels of innate immune gene expression
Time frame: 6 days
Mean YF17D viremia levels
Time frame: 14 days
Results and safety
The study was stopped early (reason given: slow recruitment due to COVID19). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2024.
- Individual participant dataSharing planned: Undecided
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Screening Protocol
Pain
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Gentamicin in people with Healthy Volunteers, run by Singapore General Hospital at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: slow recruitment due to COVID19). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of subjects with detectable YF17D viremia (time frame: 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2024.