Healthy VolunteersPhase 1CLCPDNCT04053140
Closed-loop Control of Penicillin Delivery
A Phase 1 study testing Microneedle array, Penicillin G_1200mg and Penicillin G_2400mg 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 penicillin biosensor technology linked with closed-loop control for the automated delivery of penicillin antibiotics. 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?
- Microneedle array, Penicillin G_1200mg and Penicillin G_2400mg
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 5 Nov 2019to 31 May 2024
- Phase
- Phase 1
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Adult >18 years old.
- Healthy adults, with no evidence of infection.
- Previously received penicillin with no adverse effects.
Who cannot join
- < 18 years old.
- High risk of skin and soft tissue infection or local skin and soft tissue infection near sensor site.
- Hypersensitivity to adhesive strips or active dermatitis.
- Penicillin hypersensitivity 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).
- Renal impairment on screening bloods (defined as a Cockcroft-Gault creatinine clearance <60mL/min).
Show all 9Show fewer
- Liver impairment on screening bloods (defined as ALT, ALP or bilirubin 3x ULN).
- Implantable electronic device in-situ if wearing a microneedle array device.
- Pregnant.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Closed-loop Control of Penicillin Delivery Integrating Electrochemical Biosensor Technology
This study is an in-house feasibility study of penicillin biosensor technology linked with closed-loop control for the automated delivery of penicillin antibiotics.
Read the detailed description
Outline of the study:
This study will take place at the Imperial Clinical Research Facility (ICRF). Twenty healthy volunteers will be recruited to take part in three visits to the ICRF. These will each last 8-12 hours. During these visits participants will receive penicillin via infusion following:
(i) Routine (intermittent or continuous) dosing protocols. (ii) Intermittent dosing directed by a closed-loop control system. (iii) Continuous dosing directed by a closed-loop control system. Participants will have up to 15 blood samples and tissue microdialysis performed. A biosensor will also be used to provide real-time antibiotic concentration data. This will be used to drive the closed-loop control system. Outcome measures will be PK-PD target attainment between visits. This target will be 50% time > MIC and 100% time > MIC.
Participant 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 by the Healthy Volunteer Database Administrator and individuals responding will then followed up by telephone or e-mail and invited to attend a screening visit at the ICRF. They will be sent the participant information leaflet via email in advance of this meeting to give them time to consider the information.
Study methodology:
- Twenty healthy volunteers will be invited to participate in an exploratory study of the biosensor device and closed-loop control systems.
- Allergy status will be confirmed with the participant at each visit.
- Study days will follow the same format. The only deviation will be the method of penicillin delivery (this will either be by routine infusion, closed-loop intermittent infusion, or closed-loop continuous infusion).
- On the night before study visits, participants will be asked to refrain from drinking alcohol. On the study day they will be invited to bring a laptop / tablet device for their entertainment. Alternatively, one will be provided on the study day by the ICRF.
- On arrival at the study center the participant will have a microneedle biosensor sited.
- They will have two cannulae inserted, ideally one in each arm. One of these will be for taking blood during the study. The other will be for penicillin delivery.
- They will also have a microdialysis fibre inserted in the same arm as the microneedle array.
- A baseline blood sample will be taken (full blood count, renal function, liver function, and C-reactive protein) on each visit.
- The microneedle biosensor will be sited peripherally (on the non-dominant arm). These sensors are connected to potentiostat devices that record data, which can then be downloaded onto a computer for analysis.
- The study will then commence at time = 0 when the first infusion of penicillin will be given.
- In total, the study will run for 3 benzylpenicillin dosing intervals (8-12 hours). For intermittent, routine care benzylpenicillin doses will be given at time = 0, 4, and 8 hours. During closed-loop control visits the controller will be allowed to determine the dosing interval / period. The controller will be limited to deliver a MAXIMUM dose equivalent to 2.4g every 4-hours.
- During the study interval the participant will undergo rich blood and microdialysis drug concentration sampling. For blood sampling, up to 15 beta-lactam drug levels will be taken during the study visit period. Each blood test will involve the collection of 5mLs of blood (1 teaspoon). Microdialysis will be performed continuously for the study period. The collection vial will be changed every 15-30 minutes during the study period.
- In addition, a blood spot will be used from the blood samples taken as part of the PK sampling to test point-of-care penicillin sensors at the time-points described below.
- A visual analogue scale will be completed by the participant every hour to evaluate their level of discomfort due to the microneedle sensor device. The device and site will also be checked by researchers every hour.
- Time points for the blood sampling are planned to initially be taken at pre, 6, 10, 15, 30, 60, 120, 180, 240, 246, 250, 300, 480, 486, 600 minutes. However, following initial PK analysis a D-optimal design will be employed using Pmetrics and BestDose pharmacokinetic software to determine the optimal time points for blood PK analysis.
- Conditions
- Healthy Volunteers
- Being tested
- Microneedle array, Microneedle array and closed-loop control of penicillin delivery, Penicillin G_1200mg, Penicillin G_2400mg, Penicillin G_600mg/hr
- Keywords
- Pharmacokinetics, Penicillin G, 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.
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.
Microneedle array and closed-loop control of penicillin deliveryDevice
The microneedle biosensor will be sited peripherally (on the non-dominant arm) for the duration of the study. It will then be removed. Microneedle data will be used to titrate benzylpenicillin dosage according to PK-PD target.
Penicillin G_1200mgDrug
Also called Benzylpenicillin
Benzylpenicillin IV 1200mg administered every 4 hours.
Penicillin G_2400mgDrug
Also called Benzylpenicillin
Benzylpenicillin IV administered in intermittent dosing schedule. Dosage to be determined by closed-loop algorithm. Limits set to 2400mg every 4 hours.
Penicillin G_600mg/hrDrug
Also called Benzylpenicillin
Benzylpenicillin IV administered in continuous dosing schedule. Dosage to be determined by closed-loop algorithm. Initial loading dose, and limits set to 600mg/hr.
| Study group | Role | What they receive |
|---|---|---|
| Routine intermittent slow bolus | Experimental | The microneedle biosensor will be sited peripherally (on the non-dominant arm) for the duration of the study. It will then be removed. Benzylpenicillin IV 1200mg administered every 4 hours. Receives: Device: Microneedle array; Drug: Penicillin G_1200mg |
| Closed-loop control of intermittent slow bolus | Experimental | The microneedle biosensor will be sited peripherally (on the non-dominant arm) for the duration of the study. It will then be removed. Benzylpenicillin IV administered in intermittent dosing schedule. Dosage to be determined by closed-loop algorithm. Limits set to 2400mg every 4 hours. Receives: Device: Microneedle array and closed-loop control of penicillin delivery; Drug: Penicillin G_2400mg |
| Closed-loop control of continuous infusion | Experimental | The microneedle biosensor will be sited peripherally (on the non-dominant arm) for the duration of the study. It will then be removed. Benzylpenicillin IV administered in continuous dosing schedule. Dosage to be determined by closed-loop algorithm. Initial loading dose, and limits set to 600mg/hr. Receives: Device: Microneedle array and closed-loop control of penicillin delivery; Drug: Penicillin G_600mg/hr |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of the biosensors ability to track benzylpenicillin concentrations compared to observations made by microdialysis and blood sampling.
Bland-Altman plot to describe agreement between interstitial benzylpenicillin concentrations and microneedle data.
Measured: Up to 12 hours.
Compare PK-PD target attainment between visits
Compare time > MIC between visits
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 posted12 Aug 2019
- Study start5 Nov 2019
- Primary completion31 May 2024
- Study completion31 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 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
- NCT04053140
- Sponsor's protocol ID
- 251161
- Acronym
- CLCPD
- Status last verified
- Jul 2024
- First submitted
- 24 Jul 2019
- Last updated
- 10 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gowers SAN, Freeman DME, Rawson TM, Rogers ML, Wilson RC, Holmes AH, Cass AE, O'Hare D. Development of a Minimally Invasive Microneedle-Based Sensor for Continuous Monitoring of beta-Lactam Antibiotic Concentrations in Vivo. ACS Sens. 2019 Apr 26;4(4):1072-1080. doi: 10.1021/acssensors.9b00288. Epub 2019 Apr 17.
PubMed 30950598
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Closed-loop Control of Penicillin Delivery Integrating Electrochemical Biosensor Technology
- ClinicalTrials.gov ID
- NCT04053140
- Acronym / sponsor ID
- CLCPD / 251161
- Conditions
- Healthy Volunteers
- Keywords
- Pharmacokinetics, Penicillin G, Penicillins, Proof of Concept Study, Clinical Trial, Phase I, Microneedle array
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- 5 Nov 2019 (actual)
- Primary completion
- 31 May 2024 (actual)
- Study completion
- 31 May 2024 (actual)
- First posted
- 12 Aug 2019 (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.
This study is an in-house feasibility study of penicillin biosensor technology linked with closed-loop control for the automated delivery of penicillin antibiotics.
Detailed description
Outline of the study:
This study will take place at the Imperial Clinical Research Facility (ICRF). Twenty healthy volunteers will be recruited to take part in three visits to the ICRF. These will each last 8-12 hours. During these visits participants will receive penicillin via infusion following:
(i) Routine (intermittent or continuous) dosing protocols. (ii) Intermittent dosing directed by a closed-loop control system. (iii) Continuous dosing directed by a closed-loop control system. Participants will have up to 15 blood samples and tissue microdialysis performed. A biosensor will also be used to provide real-time antibiotic concentration data. This will be used to drive the closed-loop control system. Outcome measures will be PK-PD target attainment between visits. This target will be 50% time > MIC and 100% time > MIC.
Participant 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 by the Healthy Volunteer Database Administrator and individuals responding will then followed up by telephone or e-mail and invited to attend a screening visit at the ICRF. They will be sent the participant information leaflet via email in advance of this meeting to give them time to consider the information.
Study methodology:
- Twenty healthy volunteers will be invited to participate in an exploratory study of the biosensor device and closed-loop control systems.
- Allergy status will be confirmed with the participant at each visit.
- Study days will follow the same format. The only deviation will be the method of penicillin delivery (this will either be by routine infusion, closed-loop intermittent infusion, or closed-loop continuous infusion).
- On the night before study visits, participants will be asked to refrain from drinking alcohol. On the study day they will be invited to bring a laptop / tablet device for their entertainment. Alternatively, one will be provided on the study day by the ICRF.
- On arrival at the study center the participant will have a microneedle biosensor sited.
- They will have two cannulae inserted, ideally one in each arm. One of these will be for taking blood during the study. The other will be for penicillin delivery.
- They will also have a microdialysis fibre inserted in the same arm as the microneedle array.
- A baseline blood sample will be taken (full blood count, renal function, liver function, and C-reactive protein) on each visit.
- The microneedle biosensor will be sited peripherally (on the non-dominant arm). These sensors are connected to potentiostat devices that record data, which can then be downloaded onto a computer for analysis.
- The study will then commence at time = 0 when the first infusion of penicillin will be given.
- In total, the study will run for 3 benzylpenicillin dosing intervals (8-12 hours). For intermittent, routine care benzylpenicillin doses will be given at time = 0, 4, and 8 hours. During closed-loop control visits the controller will be allowed to determine the dosing interval / period. The controller will be limited to deliver a MAXIMUM dose equivalent to 2.4g every 4-hours.
- During the study interval the participant will undergo rich blood and microdialysis drug concentration sampling. For blood sampling, up to 15 beta-lactam drug levels will be taken during the study visit period. Each blood test will involve the collection of 5mLs of blood (1 teaspoon). Microdialysis will be performed continuously for the study period. The collection vial will be changed every 15-30 minutes during the study period.
- In addition, a blood spot will be used from the blood samples taken as part of the PK sampling to test point-of-care penicillin sensors at the time-points described below.
- A visual analogue scale will be completed by the participant every hour to evaluate their level of discomfort due to the microneedle sensor device. The device and site will also be checked by researchers every hour.
- Time points for the blood sampling are planned to initially be taken at pre, 6, 10, 15, 30, 60, 120, 180, 240, 246, 250, 300, 480, 486, 600 minutes. However, following initial PK analysis a D-optimal design will be employed using Pmetrics and BestDose pharmacokinetic software to determine the optimal time points for blood PK analysis.
Study design
- Primary purpose
- Device feasibility
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Routine intermittent slow bolus | Experimental | Device: Microneedle array, Drug: Penicillin G_1200mgThe microneedle biosensor will be sited peripherally (on the non-dominant arm) for the duration of the study. It will then be removed. Benzylpenicillin IV 1200mg administered every 4 hours. |
| Closed-loop control of intermittent slow bolus | Experimental | Device: Microneedle array and closed-loop control of penicillin delivery, Drug: Penicillin G_2400mgThe microneedle biosensor will be sited peripherally (on the non-dominant arm) for the duration of the study. It will then be removed. Benzylpenicillin IV administered in intermittent dosing schedule. Dosage to be determined by closed-loop algorithm. Limits set to 2400mg every 4 hours. |
| Closed-loop control of continuous infusion | Experimental | Device: Microneedle array and closed-loop control of penicillin delivery, Drug: Penicillin G_600mg/hrThe microneedle biosensor will be sited peripherally (on the non-dominant arm) for the duration of the study. It will then be removed. Benzylpenicillin IV administered in continuous dosing schedule. Dosage to be determined by closed-loop algorithm. Initial loading dose, and limits set to 600mg/hr. |
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 adults, with no evidence of infection.
- Previously received penicillin with no adverse effects.
Key exclusion criteria (9 listed)
- < 18 years old.
- High risk of skin and soft tissue infection or local skin and soft tissue infection near sensor site.
- Hypersensitivity to adhesive strips or active dermatitis.
- Penicillin hypersensitivity 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 |
|---|---|---|
| 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 | Routine intermittent slow bolus |
| Microneedle array and closed-loop control of penicillin deliveryThe microneedle biosensor will be sited peripherally (on the non-dominant arm) for the duration of the study. It will then be removed. Microneedle data will be used to titrate benzylpenicillin dosage according to PK-PD target. | Device | Closed-loop control of continuous infusion, Closed-loop control of intermittent slow bolus |
| Penicillin G_1200mgAlso: BenzylpenicillinBenzylpenicillin IV 1200mg administered every 4 hours. | Drug | Routine intermittent slow bolus |
| Penicillin G_2400mgAlso: BenzylpenicillinBenzylpenicillin IV administered in intermittent dosing schedule. Dosage to be determined by closed-loop algorithm. Limits set to 2400mg every 4 hours. | Drug | Closed-loop control of intermittent slow bolus |
| Penicillin G_600mg/hrAlso: BenzylpenicillinBenzylpenicillin IV administered in continuous dosing schedule. Dosage to be determined by closed-loop algorithm. Initial loading dose, and limits set to 600mg/hr. | Drug | Closed-loop control of continuous infusion |
Primary outcome
Assessment of the biosensors ability to track benzylpenicillin concentrations compared to observations made by microdialysis and blood sampling.
Time frame: Up to 12 hours.
Bland-Altman plot to describe agreement between interstitial benzylpenicillin concentrations and microneedle data.
Compare PK-PD target attainment between visits
Time frame: Up to 12 hours.
Compare time > MIC between visits
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2024.
- Background: PubMed 30950598Gowers SAN, Freeman DME, Rawson TM, Rogers ML, Wilson RC, Holmes AH, Cass AE, O'Hare D. Development of a Minimally Invasive Microneedle-Based Sensor for Continuous Monitoring of beta-Lactam Antibiotic Concentrations in Vivo. ACS Sens. 2019 Apr 26;4(4):1072-1080. doi: 10.1021/acssensors.9b00288. Epub 2019 Apr 17.
- Minimally Invasive Sensing of Beta-lactam Antibiotics (MISBL)Link provided by the sponsor.
- 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 Microneedle array, Penicillin G_1200mg and Penicillin G_2400mg 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 9 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 10 Jul 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 benzylpenicillin concentrations compared to observations made by microdialysis and blood sampling. (time frame: Up to 12 hours.). The study lists 2 primary outcomes in all. 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 NCT04053140, 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 10 Jul 2024.