Healthy VolunteersPhase 1MISBLNCT03847610
Minimally Invasive Sensing of Beta-lactam Antibiotics
A Phase 1 study testing Phenoxymethyl Penicillin and Microneedle array in people with Healthy Volunteers, run by Imperial College London at 1 site in United Kingdom.
Trial summary
This study is an in-house feasibility study of a microneedle biosensor developed within Imperial College London. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Phenoxymethyl Penicillin and Microneedle array
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 12 Apr 2018to 10 Aug 2018
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Adult >18 years old
- Healthy with no evidence of active infection
- Previously received penicillin with no adverse effects
Who cannot join
- High risk of skin soft tissue infection or local skin and soft tissue infection near sensor site
- Previous history of allergies to adhesive strips or active dermatitis
- Penicillin allergy or previous adverse event whilst receiving penicillin
- Anaemia on screening bloods (defined as haemoglobin <13 g/dL in males and <12 g/dL in females)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Microneedle Sensing of Beta-lactam Antibiotic Concentrations in Human Interstitial Fluid
This study is an in-house feasibility study of a microneedle biosensor developed within Imperial College London.
Read the detailed description
Outline of the study:
This study will comprise the recruitment of 10-15 healthy volunteers. They will be recruited to test the microneedle biosensors and undergo rich plasma sampling with or without tissue microdialysis to calibrate the microneedle biosensor and evaluate its accuracy against current gold standards (i.e. plasma drug concentration and tissue microdialysis). This study will take place at the Imperial Clinical Research Facility (CRF).
Patient identification:
Healthy volunteers will be recruited from a healthy volunteer database held within Imperial College London and via identification of participants within the College. An initial advertisement e-mail will be sent and individuals responding will then followed up by telephone and invited to attend a screening visit at the Imperial CRF. They will be sent the participant information leaflet in advance of this meeting to give them time to consider the information. At this visit a member of the research team will go through the study procedure and answer any questions that the participant has.
Consent procedure:
Healthy volunteers who wish to participate in the study after considering the participant information leaflet will be consented by a trained researcher who will complete the eligibility screening for inclusion into the study.
Study Methodology:
10-15 healthy volunteers will be invited to participate in an exploratory study of the sensor device. On their screening visit routine blood tests will be performed to ensure that the participant is not anaemic and has no evidence of current infection. Before the study day the participant will be required to take 5 doses of oral penicillin to ensure that they are at steady state and to allow for stabilization of tissue distribution. Four of these doses will be taken at 6-hour intervals on the day before they attend the Imperial CRF. The final dose will be taken on the morning that they attend.
On arrival at the study centre the participant will have a microneedle biosensor sited for up to 12 hours whilst receiving antimicrobial therapy. The sensor will be sited peripherally (on an arm or leg). In a small number of cases the sensor may be sited centrally on the torso. These sensors are connected to potentiostat devices that records data, which can then be downloaded onto a computer for analysis.
Following arrival on the study day and placing of the sensor devices, a cannula will be sited for phlebotomy and a baseline beta-lactam antibiotic concentration will be taken. A microdialysis fibre will also be inserted peripherally into tissue close to the microneedle device to allow gold standard analysis of tissue antibiotic concentration. The participant will then undergo rich plasma drug sampling with up to 15 blood tests taken over a 6-12 hour period.
Each blood test will involve the collection of 3mL extra blood (<1 teaspoons) via a cannula which will be cited on commencement of the study. Microdialysis may be performed in all participants who consent to this as a gold standard for determining tissue drug concentrations. If they do not consent for this, the study will be able to continue without microdialysis being performed. Participants will also be required to complete a visual analogue scale every hour testing their level of discomfort due to the microneedle sensor device and a member of the research team will document any redness or skin changes around the site of the device. A further dose of penicillin will be given approximately 6 hours into the study.
Time points for the blood sampling are planned to initially be taken at (0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240, 360, 480, 600, 720 minutes). However, following initial pharmacokinetic (PK) analysis a D-optimal design will be employed using Pmetrics and BestDose PK software to determine the optimal time points for blood PK analysis. This will be performed by a trained member of the research team.
Clinically relevant data including demographic, co-morbidity, and medication data will be collected by members of the research team from the participant.
- Conditions
- Healthy Volunteers
- Being tested
- Phenoxymethyl Penicillin, Microneedle array
- Keywords
- Pharmacokinetics, Penicillin V, Penicillins, Proof of Concept Study, Clinical Trial, Phase I, Microneedle array
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Phenoxymethyl PenicillinDrug
Phenoxymethylpenicillin tablets, 500mg every six hours for six doses, starting the day before study
Microneedle arrayDevice
The microneedle biosensor will be sited peripherally (on the non-dominant arm) for the duration of the study. It will then be removed.
| Study group | Role | What they receive |
|---|---|---|
| Healthy volunteer | Experimental | Not described Receives: Drug: Phenoxymethyl Penicillin; Device: Microneedle array |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of the Biosensors Ability to Track Phenoxymethylpenicillin Concentrations Compared to Observations Made by Microdialysis and Blood Sampling
Bland-Altman plot to describe agreement between interstitial phenoxymethylpenicillin concentrations and microneedle data (mean difference between microneedle and microdialysis measurements)
Measured: Up to 12 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2019
- Study start12 Apr 2018
- Primary completion10 Aug 2018
- Study completion10 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe 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 1
- Primary purpose
- Device feasibility
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alison H Holmes, MD MPH MBBS, Principal investigator, Health Protection Research Unit in HCAI & AMR
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03847610
- Sponsor's protocol ID
- 17IC4051
- Other IDs
- 236047, 18/LO/0054
- Acronym
- MISBL
- Status last verified
- Mar 2024
- First submitted
- 7 Feb 2019
- Last updated
- 27 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Rawson TM, Gowers SAN, Freeman DME, Wilson RC, Sharma S, Gilchrist M, MacGowan A, Lovering A, Bayliss M, Kyriakides M, Georgiou P, Cass AEG, O'Hare D, Holmes AH. Microneedle biosensors for real-time, minimally invasive drug monitoring of phenoxymethylpenicillin: a first-in-human evaluation in healthy volunteers. Lancet Digit Health. 2019 Nov;1(7):e335-e343. doi: 10.1016/S2589-7500(19)30131-1. Epub 2019 Sep 30.
PubMed 33323208
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Microneedle Sensing of Beta-lactam Antibiotic Concentrations in Human Interstitial Fluid
- ClinicalTrials.gov ID
- NCT03847610
- Acronym / sponsor ID
- MISBL / 17IC4051
- Conditions
- Healthy Volunteers
- Keywords
- Pharmacokinetics, Penicillin V, Penicillins, Proof of Concept Study, Clinical Trial, Phase I, Microneedle array
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- 12 Apr 2018 (actual)
- Primary completion
- 10 Aug 2018 (actual)
- Study completion
- 10 Aug 2018 (actual)
- First posted
- 20 Feb 2019 (actual)
- Results
- Posted 29 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is an in-house feasibility study of a microneedle biosensor developed within Imperial College London.
Detailed description
Outline of the study:
This study will comprise the recruitment of 10-15 healthy volunteers. They will be recruited to test the microneedle biosensors and undergo rich plasma sampling with or without tissue microdialysis to calibrate the microneedle biosensor and evaluate its accuracy against current gold standards (i.e. plasma drug concentration and tissue microdialysis). This study will take place at the Imperial Clinical Research Facility (CRF).
Patient identification:
Healthy volunteers will be recruited from a healthy volunteer database held within Imperial College London and via identification of participants within the College. An initial advertisement e-mail will be sent and individuals responding will then followed up by telephone and invited to attend a screening visit at the Imperial CRF. They will be sent the participant information leaflet in advance of this meeting to give them time to consider the information. At this visit a member of the research team will go through the study procedure and answer any questions that the participant has.
Consent procedure:
Healthy volunteers who wish to participate in the study after considering the participant information leaflet will be consented by a trained researcher who will complete the eligibility screening for inclusion into the study.
Study Methodology:
10-15 healthy volunteers will be invited to participate in an exploratory study of the sensor device. On their screening visit routine blood tests will be performed to ensure that the participant is not anaemic and has no evidence of current infection. Before the study day the participant will be required to take 5 doses of oral penicillin to ensure that they are at steady state and to allow for stabilization of tissue distribution. Four of these doses will be taken at 6-hour intervals on the day before they attend the Imperial CRF. The final dose will be taken on the morning that they attend.
On arrival at the study centre the participant will have a microneedle biosensor sited for up to 12 hours whilst receiving antimicrobial therapy. The sensor will be sited peripherally (on an arm or leg). In a small number of cases the sensor may be sited centrally on the torso. These sensors are connected to potentiostat devices that records data, which can then be downloaded onto a computer for analysis.
Following arrival on the study day and placing of the sensor devices, a cannula will be sited for phlebotomy and a baseline beta-lactam antibiotic concentration will be taken. A microdialysis fibre will also be inserted peripherally into tissue close to the microneedle device to allow gold standard analysis of tissue antibiotic concentration. The participant will then undergo rich plasma drug sampling with up to 15 blood tests taken over a 6-12 hour period.
Each blood test will involve the collection of 3mL extra blood (<1 teaspoons) via a cannula which will be cited on commencement of the study. Microdialysis may be performed in all participants who consent to this as a gold standard for determining tissue drug concentrations. If they do not consent for this, the study will be able to continue without microdialysis being performed. Participants will also be required to complete a visual analogue scale every hour testing their level of discomfort due to the microneedle sensor device and a member of the research team will document any redness or skin changes around the site of the device. A further dose of penicillin will be given approximately 6 hours into the study.
Time points for the blood sampling are planned to initially be taken at (0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240, 360, 480, 600, 720 minutes). However, following initial pharmacokinetic (PK) analysis a D-optimal design will be employed using Pmetrics and BestDose PK software to determine the optimal time points for blood PK analysis. This will be performed by a trained member of the research team.
Clinically relevant data including demographic, co-morbidity, and medication data will be collected by members of the research team from the participant.
Study design
- Primary purpose
- Device feasibility
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Healthy volunteer | Experimental | Drug: Phenoxymethyl Penicillin, Device: Microneedle array |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adult >18 years old
- Healthy with no evidence of active infection
- Previously received penicillin with no adverse effects
Key exclusion criteria (4 listed)
- High risk of skin soft tissue infection or local skin and soft tissue infection near sensor site
- Previous history of allergies to adhesive strips or active dermatitis
- Penicillin allergy or previous adverse event whilst receiving penicillin
- Anaemia on screening bloods (defined as haemoglobin <13 g/dL in males and <12 g/dL in females)
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 |
|---|---|---|
| Phenoxymethyl PenicillinPhenoxymethylpenicillin tablets, 500mg every six hours for six doses, starting the day before study | Drug | Healthy volunteer |
| Microneedle arrayThe microneedle biosensor will be sited peripherally (on the non-dominant arm) for the duration of the study. It will then be removed. | Device | Healthy volunteer |
Primary outcome
Assessment of the Biosensors Ability to Track Phenoxymethylpenicillin Concentrations Compared to Observations Made by Microdialysis and Blood Sampling
Time frame: Up to 12 hours
Bland-Altman plot to describe agreement between interstitial phenoxymethylpenicillin concentrations and microneedle data (mean difference between microneedle and microdialysis measurements)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33323208Rawson TM, Gowers SAN, Freeman DME, Wilson RC, Sharma S, Gilchrist M, MacGowan A, Lovering A, Bayliss M, Kyriakides M, Georgiou P, Cass AEG, O'Hare D, Holmes AH. Microneedle biosensors for real-time, minimally invasive drug monitoring of phenoxymethylpenicillin: a first-in-human evaluation in healthy volunteers. Lancet Digit Health. 2019 Nov;1(7):e335-e343. doi: 10.1016/S2589-7500(19)30131-1. Epub 2019 Sep 30.
- Individual participant dataSharing planned: No
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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.
Alison H Holmes, MD MPH MBBS principal investigator
Health Protection Research Unit in HCAI & AMR
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Phenoxymethyl Penicillin and Microneedle array in people with Healthy Volunteers, run by Imperial College London at 1 site in United Kingdom.
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 3 inclusion and 4 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: finished, as of the sponsor's last update on 27 Mar 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 United Kingdom. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Assessment of the Biosensors Ability to Track Phenoxymethylpenicillin Concentrations Compared to Observations Made by Microdialysis and Blood Sampling (time frame: Up to 12 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03847610, which also lists 1 linked publication.
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 27 Mar 2024.