MISBL: Minimally Invasive Sensing of Beta-lactam Antibiotics

• Sponsor: Imperial College London (Other)
• Overall Status: Completed
• CT.gov ID: NCT03847610
• Collaborator: (none)
• Enrollment: 11
• Location: 1
• Arm: 1
• Actual Duration (Months): 3.9
• Patients Per Site Per Month: 2.8

Study Details

Study Description

Brief Summary

This study is an in-house feasibility study of a microneedle biosensor developed within Imperial College London.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: Phenoxymethyl Penicillin; Device: Microneedle array	Phase 1

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

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Device Feasibility
• Official Title: Microneedle Sensing of Beta-lactam Antibiotic Concentrations in Human Interstitial Fluid
• Actual Study Start Date: Apr 12, 2018
• Actual Primary Completion Date: Aug 10, 2018
• Actual Study Completion Date: Aug 10, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Healthy volunteer	Drug: Phenoxymethyl Penicillin; Phenoxymethylpenicillin tablets, 500mg every six hours for six doses, starting the day before study; Device: Microneedle array; The microneedle biosensor will be sited peripherally (on the non-dominant arm) for the duration of the study. It will then be removed.

Outcome Measures

Primary Outcome Measures

1. Assessment of the Biosensors Ability to Track Phenoxymethylpenicillin Concentrations Compared to Observations Made by Microdialysis and Blood Sampling [Up to 12 hours]

   Bland-Altman plot to describe agreement between interstitial phenoxymethylpenicillin concentrations and microneedle data (mean difference between microneedle and microdialysis measurements)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Adult >18 years old

• Healthy with no evidence of active infection

• Previously received penicillin with no adverse effects

Exclusion Criteria:

• 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	NIHR Imperial CRF	London		United Kingdom	W12 0HS

Sponsors and Collaborators

• Imperial College London

Investigators

• Principal Investigator: Alison H Holmes, MD MPH MBBS, Health Protection Research Unit in HCAI & AMR

Study Documents (Full-Text)

• Study Protocol - Dec 6, 2017

More Information

Publications

None provided.

• Responsible Party: Imperial College London
• ClinicalTrials.gov Identifier: NCT03847610
• Other Study ID Numbers: 17IC4051; 236047; 18/LO/0054
• First Posted: Feb 20, 2019
• Last Update Posted: Dec 29, 2020
• Last Verified: Dec 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Imperial College London: Pharmacokinetics; Penicillin V; Penicillins; Proof of Concept Study; Clinical Trial, Phase I; Microneedle array
• Additional relevant MeSH terms: Penicillins; Penicillin V

Study Results

Participant Flow

Pre-assignment Detail	One volunteer withdrew consent to undergo microdialysis on the study day and was withdrawn from the analysis. The participant did not cite a reason for declining microdialysis catheter insertion. Therefore, ten volunteers were included in the study.

Arm/Group Title	Healthy Volunteer
Arm/Group Description	Phenoxymethyl Penicillin: Phenoxymethylpenicillin tablets, 500mg every six hours for six doses, starting the day before study Microneedle array: The microneedle biosensor will be sited peripherally (on the non-dominant arm) for the duration of the study. It will then be removed.
Period Title: Overall Study
STARTED	11
COMPLETED	10
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Healthy Volunteer
Arm/Group Description	Phenoxymethyl Penicillin: Phenoxymethylpenicillin tablets, 500mg every six hours for six doses, starting the day before study Microneedle array: The microneedle biosensor will be sited peripherally (on the non-dominant arm) for the duration of the study. It will then be removed.
Overall Participants	10
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42 (14)
Sex: Female, Male (Count of Participants)
Female	3 30%
Male	7 70%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
United Kingdom	10 100%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	24 (3)
Creatinine clearance (mL/min) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL/min]	114 (29)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	174 (11)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	74 (15)

Outcome Measures

1. Primary Outcome

Title	Assessment of the Biosensors Ability to Track Phenoxymethylpenicillin Concentrations Compared to Observations Made by Microdialysis and Blood Sampling
Description	Bland-Altman plot to describe agreement between interstitial phenoxymethylpenicillin concentrations and microneedle data (mean difference between microneedle and microdialysis measurements)
Time Frame	Up to 12 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Healthy Volunteer
Arm/Group Description	Phenoxymethyl Penicillin: Phenoxymethylpenicillin tablets, 500mg every six hours for six doses, starting the day before study Microneedle array: The microneedle biosensor will be sited peripherally (on the non-dominant arm) for the duration of the study. It will then be removed.
Measure Participants	10
Mean (95% Confidence Interval) [mg/L]	-0.16

Adverse Events

Time Frame	Study day -1, and on the study day for each participant
Arm/Group Title	Healthy Volunteer
Arm/Group Description	Phenoxymethyl Penicillin: Phenoxymethylpenicillin tablets, 500mg every six hours for six doses, starting the day before study Microneedle array: The microneedle biosensor will be sited peripherally (on the non-dominant arm) for the duration of the study. It will then be removed.
All Cause Mortality
	Healthy Volunteer
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Serious Adverse Events
	Healthy Volunteer
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Other (Not Including Serious) Adverse Events
	Healthy Volunteer
	Affected / at Risk (%)	# Events
Total	0/10 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.