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Trial registered on ANZCTR


Registration number
ACTRN12620000701921p
Ethics application status
Submitted, not yet approved
Date submitted
18/05/2020
Date registered
26/06/2020
Date last updated
25/10/2021
Date data sharing statement initially provided
26/06/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Safety and tolerance of manuka honey for use as a nebulizer solution
Scientific title
Safety and tolerance of manuka honey for use as a nebulizer solution in a group of healthy volunteers
Secondary ID [1] 301275 0
None
Universal Trial Number (UTN)
Trial acronym
MANFFT-02
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Respiratory diseases 317453 0
Infectious diseases 317651 0
Condition category
Condition code
Respiratory 315551 315551 0 0
Other respiratory disorders / diseases
Infection 315736 315736 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Up to 15 subjects will be recruited and each will be required to sequentially take sterile saline (control), 3.13, 6.25, 12.5, 25 and 50% v/v medical grade manuka honey in a nebuliser solution for 10 min.

Subjects will be tested at either the Ruakura Research Centre (Hamilton), or at the ManukaMed facility (Masterton). Participants will self-administer the doses under the supervision of the principle investigator. One of each of the doses will be administered on successive days for a total of 6 days.

The nebulizer is a jet (compressor) type that delivers 0.3 mL per min with a mean particle diameter of 3 uM (model C801, Omron Healthcare Ltd, Kyoto, Japan). Therefore, subjects will breath 3 mL over the 10 min period. The volume administered during the 10 min period will be the product of the volume added minus the volume remaining after 10 min.

The nebulizer has not been approved for this use, nor has approval been sought by either the manufacturer, or the New Zealand Medicines and Medical Devices Safety Authority.

During the 10 min treatment period, subjects will wear a silicone face mask provided with the nebulizer.
Intervention code [1] 317581 0
Treatment: Other
Intervention code [2] 317582 0
Treatment: Drugs
Intervention code [3] 317583 0
Treatment: Devices
Comparator / control treatment
sterile saline 0.9% w/v
Control group
Placebo

Outcomes
Primary outcome [1] 323795 0
Any change in SpO2 between baseline and post-treatment time-point measurements using a pulse oximeter for 30 seconds.
Timepoint [1] 323795 0
0 (baseline), 1, 3, 6 and 24 h post-dose administration on each test day.
Primary outcome [2] 323948 0
Any change in lung performance (Forced Vital Capacity (FVC), Forced Expiratory Volume (FEV1), FEV1/FVC x 100 (FEV1%), Average Forced Expiratory Flow between 25 and 75% (FEF2575) and Peak Expiratory Flow (PEF)) as measured using a spirometer between baseline and post-treatment time-point measurements. This is a composite primary outcome.
Timepoint [2] 323948 0
0 (baseline), 1, 3, 6 and 24 h post-dose administration on each test day.
Primary outcome [3] 323949 0
Any change in vital signs (heart rate, respiratory rate, temperature and blood pressure) between baseline and post-treatment time-point measurements.

Heart rate will be measured using a pulse oximeter for 30 seconds at each time-point, respiratory rate will be measured by countered the breaths for 15 seconds and multiplying by 4, temperature will be measured using an infrared contactless thermometer and blood pressure will be measured using a sphygmomanometer (Omron Healthcare Ltd). This is a composite primary outcome
Timepoint [3] 323949 0
0 (baseline), 1, 3, 6 and 24 h post-dose administration on each test day.
Secondary outcome [1] 382921 0
Participant preference/tolerability of each dosage will be assessed daily after administration of the intervention using a study-specific questionnaire that will evaluate stickiness, flavour and odour on a n-point scale. This is a composite secondary outcome.
Timepoint [1] 382921 0
At 6h post-dose administration on each test day.
Secondary outcome [2] 383717 0
Any Adverse and/or Serious Adverse Events reported by the subject, or observed by the investigator will be recorded. This is a composite secondary outcome.

A list of potential adverse events is included in the protocol and the CI will prompt the subject at each visit time-point if they are feeling unwell, or have noticed any of those potential AE or SAEs. Every AE, or SAE will be assessed by the CI or Co-CI for severity and relatedness to study products.
Timepoint [2] 383717 0
O, 3, 6 and 24 h after nebulization. Subjects will be able to contact the investigator at any time up to 7 d post-study. The investigator will also follow-up with each subject 7 d after the study.

Eligibility
Key inclusion criteria
1. Be able and willing to give written informed consent,
2. Understand and comply with the requirements of the study, and be judged suitable for the study in the opinion of the Investigator,
3. Male and female subjects who are 18 to 80 years of age,
4. Subjects are not currently ill, or have a history of respiratory or cardiac disease,
5. Have vital signs that are within the normal range at time of screening (blood pressure 90/60 to 120/80 mm Hg; pulse 60-100 beats per min; breathing 12-20 breaths per min; temperature 36.5 to 37.3 °C),
6. Have lung performance parameters that are within the predicted range for their age and sex at time of screening (European Respiratory Society (ERS), European Community for Coal and Steel (ECCS)/Knudson) provided by the spirometer software (WinspiroPRO).
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Subjects who are hypersensitive, or have an allergic reaction to honey, or bee products.
2. Subjects who are on medication that may influence pulmonary measurements.
3. Subjects who are asthmatics.
4. Subjects who are ill (including common cold) on the day, or for the previous week(s).
5. Subject has a history or presence of significant cardiovascular disease, including having a cardiac pacemaker,
6. Subject has a significant acute or chronic coexisting illness which in the opinion of the investigator, could affect the outcome of the study, including kidney, liver or renal disease/dysfunction, uncontrolled metabolic disease,
7. Subject has a history of hypertension or elevated blood pressure (systolic, >140 mmHg or a diastolic, >90 mmHg), unless on stable anti-hypertensive medication for at least 3 months prior to and for the duration of the study,
8. Subject has a history of drug and / or alcohol abuse,
9. Individuals who, in the opinion of the investigator, are considered to be poor attendees or unlikely for any reason to be able to comply with the trial.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Other
Other design features
Dose-escalating safety study with subjects offered six different concentrations of manuka honey mixed in sterile saline at 0, 3.13, 6.25, 12.5, 25 and 50% v/v with one treatment offered each test day from lowest to highest dose.
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
Sample size was determined by requiring a detectable difference of 15% with a coefficient of variation of 10% at a power of 80% and with a probability of 0.05% for each parameter. The sample size required for the study is 8. At a probability of 0.01% the sample size increases to 15. However, with the possibility of subjects not completing the study, or dropping out before the study commences, we have increased the number of subjects to 15 with an equal number of males and females to be recruited.

Analysis of variance will be used to analyse the data in the software package Prism v8.4 (Graphpad Software LLC).

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Other reasons/comments
Other reasons
Did not gain ethical approval
Date of first participant enrolment
Anticipated
13/07/2020
Actual
Date of last participant enrolment
Anticipated
31/08/2020
Actual
Date of last data collection
Anticipated
28/09/2020
Actual
Sample size
Target
15
Accrual to date
Final
Recruitment outside Australia
Country [1] 22560 0
New Zealand
State/province [1] 22560 0
Waikato, Auckland, Wairarapa

Funding & Sponsors
Funding source category [1] 305722 0
Commercial sector/Industry
Name [1] 305722 0
ManukaMed LP
Country [1] 305722 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
ManukaMed LP
Address
3 Edwin Feist Place, Solway, Masterton, 5810
Country
New Zealand
Secondary sponsor category [1] 306144 0
None
Name [1] 306144 0
Address [1] 306144 0
Country [1] 306144 0
Other collaborator category [1] 281311 0
University
Name [1] 281311 0
Waikato University
Address [1] 281311 0
Private Bag 3105
Hamilton 3240
Country [1] 281311 0
New Zealand

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 305997 0
Northern A Health and Disability Ethics Committee
Ethics committee address [1] 305997 0
Ethics committee country [1] 305997 0
New Zealand
Date submitted for ethics approval [1] 305997 0
21/05/2020
Approval date [1] 305997 0
Ethics approval number [1] 305997 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 102358 0
Dr Chris McMahon
Address 102358 0
ManukaMed LP
Ruakura Research Centre
10 Bisley Rd,
Hamilton 3214
Country 102358 0
New Zealand
Phone 102358 0
+64 0210795110
Fax 102358 0
Email 102358 0
[email protected]
Contact person for public queries
Name 102359 0
Chris McMahon
Address 102359 0
ManukaMed LP
Ruakura Research Centre
10 Bisley Rd,
Hamilton 3214
Country 102359 0
New Zealand
Phone 102359 0
+64 0210795110
Fax 102359 0
Email 102359 0
[email protected]
Contact person for scientific queries
Name 102360 0
Chris McMahon
Address 102360 0
ManukaMed LP
Ruakura Research Centre
10 Bisley Rd,
Hamilton 3214
Country 102360 0
New Zealand
Phone 102360 0
+64 0210795110
Fax 102360 0
Email 102360 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data will remain confidential until and Patent Cooperation Treaty (PCT) has been filed.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.