Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000843156
Ethics application status
Approved
Date submitted
25/05/2019
Date registered
12/06/2019
Date last updated
12/06/2019
Date data sharing statement initially provided
12/06/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
An evaluation of the effects of a topical traditional Chinese medicine formulation on muscle soreness associated with athletic training
Scientific title
The efficacy of a topical traditional Chinese medicine formulation Cheong Kun Oil for reducing delayed onset muscle soreness in well trained individuals
Secondary ID [1] 298323 0
NIL
Universal Trial Number (UTN)
U1111-1234-0532
Trial acronym
Linked study record
No linked study

Health condition
Health condition(s) or problem(s) studied:
delayed muscle soreness related to exercise 312960 0
Condition category
Condition code
Musculoskeletal 311468 311468 0 0
Other muscular and skeletal disorders
Alternative and Complementary Medicine 311470 311470 0 0
Herbal remedies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This project will evaluate the efficacy of a traditional Chinese medicine Cheong Kun Oil for reducing delayed onset muscle soreness (DOMS), the muscular pain and discomfort commonly experienced after a bout of unaccustomed exercise or activity. Cheong Kun Oil is a topical preparation which has been marketed in Macau since the 1960’s for its beneficial effects on muscle pain due to exercise, strains and injuries. This study will scientifically investigate the efficacy of Cheong Kun Oil for reducing DOMS in the thigh muscles after eccentric exercise (exercise where the muscle is lengthened) in healthy, young, well trained males.
Design: Randomised, double-blind placebo controlled trial.
Intervention
As this study is a cross over design, the intervention below will be repeated twice (once on each leg) separated by 6 weeks to minimise the repeated bout effect (the familiarisation session will only occur once). A 6 week wash out period was chosen, as it has been reported that 6 weeks between eccentric exercise trials was effective to wash out any systemic inflammatory responses that would have developed in the first trial, and this wash-out period has been used successfully in other DOMS related studies. Participants will be stratified based on leg dominance before being randomized to the active or placebo group by a computer generated randomization chart that will be compiled by an independent researcher.
Study Overview
Session 1: collection of basic demographic details and familiarisation of all outcome measures (detailed below). Time commitment: 1 hour
Session 2: Baseline testing (all outcome measures), eccentric exercise protocol, post testing (all outcome measures). Time commitment: 2 hours
Session 3: 4 hours post baseline testing, all outcome measures will be reassessed. Time commitment: 30 min
Session 4: 24 hours post baseline testing, all outcome measures will be reassessed. Time commitment: 30 min
Session 5: 48 hours post baseline testing, all outcome measures will be reassessed. Time commitment: 30 min
Session 6: 72 hours post baseline testing, all outcome measures will be reassessed. Time commitment: 30 min
Session 7: 96 hours post baseline testing, all outcome measures will be reassessed. Time commitment: 30 min

Methodology Details
Session 1:
After a full explanation of the study protocol, participants will be asked to complete stage 1 of the ESSA pre-exercise screening tool, provide written informed consent, and have their body mass, height and training history recorded. The participants dominant leg will be recorded, which will be used for stratification of participants prior to randomisation. Participant will be taken through the following outcome measures which will be assessed at all time points throughout the study:
Primary Outcome measure
Muscle pain: Pain will be assessed using a visual analogue scale (VAS) in the subject’s quadriceps. The VAS will be presented on an A4 piece of paper with a 100mm line printed in the middle of the page. The line will range from 0 (no pain) to 100 mm (worst possible pain) Participants will be asked to complete a body weight squat, and rate their muscle soreness. A body weight squat will be utilised, as there is generally no pain experienced due to unaccustomed activity such as eccentric exercise when the muscles are not actively engaged in movement. This subjective pain assessment has been used by numerous studies as a reliable and valid method of assessing acute pain.

Secondary Outcome Measures

Muscle Damage: Will be assessed through salivary creatine kinase, and indicative marker of exercise induced muscle damage. Passive drool saliva samples will be collected at all time points to assess the extent of muscle damage as identified through changes to creatine kinase levels. Saliva will be collected in sterilised cryovials via passive drool using saliva collection aids (Salimetrics) and stored in -20 °C freezer.

Muscle tenderness: A pressure algometer will be used to monitor pressure induced pain at five specific sites on the quadriceps. Specific sites for assessment were determined using a reference system involving two anatomical points [anterior superior iliac spine (ASIS) and superior pole of the patella (SPP)]. All measurements will be taken on the right side whilst the participants lay supine on a plinth The measured sites will be: 15 cm distal to the ASIS, 4 cm proximal to the SPP, midpoint of the ASIS and SPP along the axis, then 2 cm lateral and 2 cm medial of this midpoint. These points of assessment were validated by a reliability study conducted by CI Pumpa, and the algometer has been validated in other studies.

Muscle function: Maximal force generating capacity will be measured as maximal isokinetic concentric and eccentric knee extension peak torque at 60°·sec-1. Participants will complete 3 maximal isokinetic concentric muscle contractions, separated by 1 min on both the intervention and control leg, before completing 3 maximal isokinetic eccentric muscle contractions, separated by 1 min on both the intervention and control leg. This assessment of muscle function has been deemed valid and reliable.

Range of Motion: Range of motion (ROM) at the hip and knee joints will be assessed using a goniometer. A goniometer is a non-invasive standard device for measuring angles, Passive hip and knee flexion and extension will be assessed on all participants using standardised protocols. Three trials for each movement will be recorded, and the median value used for analysis.
Inflammation: An anthropometric measuring tape will be used to measure mid-thigh circumference, the midpoint between the anthropometric sites trochanterion and tibiale laterale. Circumference measurements will be used as an indicator of acute changes in thigh volume likely to occur from osmotic fluid shifts or inflammation, which is often associated with muscle damage and eccentric exercise.

To identify adverse skin reactions, the repeated open application test (ROAT) will be employed in this study. This visual assessment test is commonly employed to evaluate whether a topical application results the development of red skin, dry skin, itching or frank dermatitis that are all indicate varying degrees of allergy.

Session 2
All outcome measures noted above will be replicated before and immediately after the following the muscle damage protocol.
Participants will perform a protocol consisting of 300 eccentric unlilateral repetitions (20 sets, 15 reps per set with 30 seconds between sets) with the quadriceps muscle group at a speed of 30°·sec-1. The protocol has been shown to effectively induce myofibrillar disruption and induce DOMS.
After the post eccentric exercise assessments, participants will receive a 38mL bottle of Cheong Kun oil (or placebo), after being randomized to the active or placebo group by a computer generated randomization chart that will be compiled by an independent researcher. The oils will be provided in a plain opaque bottle with the subjects name and application regime displayed. The tubes and labeling will be completed by an individual not involved with the project, and the oil within the tubes will be identical in appearance and texture to ensure double blinding. The following directions will be printed on the label:
For Topical application only
1. Apply 5 drops of oil onto affected area ONCE daily before bed prior to each training session for 6 days (evening before session 2-7)
2. The oil had to be rubbed with massage in circular motion for 5 mins
3. Until feeling of heat sensation and the oil is completely absorbed
Participants will be asked at each follow-up session regarding the application of the oil the previous evening, and each tube will be weighed before distribution, and reweighted at the 96 hour time point to double-check compliance.

Sessions 3-7
Participants will return to the laboratory to complete all assessments associated with the outcome measures noted above but on the opposite leg.
Intervention code [1] 314560 0
Treatment: Other
Intervention code [2] 314561 0
Rehabilitation
Comparator / control treatment
After the post eccentric exercise assessments, participants will receive a 38mL bottle of Cheong Kun oil (or placebo - canola oil), after being randomized to the active or placebo group by a computer generated randomization chart that will be compiled by an independent researcher. The oils will be idenitical in packaging and appearance and will be provided in a plain opaque bottle with the subjects name and application regime displayed. The tubes and labeling will be completed by an individual not involved with the project, and the oil within the tubes will be identical in appearance and texture to ensure double blinding. The following directions will be printed on the label:
For Topical application only
1. Apply 5 drops of oil onto affected area ONCE daily before bed (evening prior to session 2-7)
2. The oil had to be rubbed with massage in circular motion for 5 mins
3. Until feeling of heat sensation and the oil is completely absorbed
Participants will be asked at each follow-up session regarding the application of the oil the previous evening, and each tube will be weighed before distribution, and reweighted at the 96 hour time point to double-check compliance.
Control group
Placebo

Outcomes
Primary outcome [1] 320175 0
Muscle pain: Pain will be assessed using a visual analogue scale (VAS) in the subject’s quadriceps. The VAS will be presented on an A4 piece of paper with a 100mm line printed in the middle of the page. The line will range from 0 (no pain) to 100 mm (worst possible pain) Participants will be asked to complete a body weight squat, and rate their muscle soreness. A body weight squat will be utilised, as there is generally no pain experienced due to unaccustomed activity such as eccentric exercise when the muscles are not actively engaged in movement. This subjective pain assessment has been used by numerous studies as a reliable and valid method of assessing acute pain
Timepoint [1] 320175 0
Baseline, 4 hours, 24 hours, 48 hours, 72 hours, 96 hours (primary timepoint)
Secondary outcome [1] 370771 0
Muscle Damage: Will be assessed through salivary creatine kinase, and indicative marker of exercise induced muscle damage. Passive drool saliva samples will be collected at all time points to assess the extent of muscle damage as identified through changes to creatine kinase levels. Saliva will be collected in sterilised cryovials via passive drool using saliva collection aids (Salimetrics) and stored in -20 °C freezer.
Timepoint [1] 370771 0
The secondary endpoints will also be repeated 6 weeks later (after wash out) but using the opposite leg. Baseline 4 hours 24 hours 48 hours 72 hours 96 hours
Secondary outcome [2] 370772 0
Muscle tenderness: A pressure algometer will be used to monitor pressure induced pain at five specific sites on the quadriceps. Specific sites for assessment were determined using a reference system involving two anatomical points [anterior superior iliac spine (ASIS) and superior pole of the patella (SPP)]. All measurements will be taken on the right side whilst the participants lay supine on a plinth The measured sites will be: 15 cm distal to the ASIS, 4 cm proximal to the SPP, midpoint of the ASIS and SPP along the axis, then 2 cm lateral and 2 cm medial of this midpoint. These points of assessment were validated by a reliability study conducted by CI Pumpa, and the algometer has been validated in other studies
Timepoint [2] 370772 0
Baseline 4 hours 24 hours 48 hours 72 hours 96 hours
Secondary outcome [3] 370773 0
Muscle function: A pressure algometer will be used to measure muscle function. Maximal force generating capacity will be measured as maximal isokinetic concentric and eccentric knee extension peak torque at 60°·sec-1. Participants will complete 3 maximal isokinetic concentric muscle contractions, separated by 1 min on both the intervention and control leg, before completing 3 maximal isokinetic eccentric muscle contractions, separated by 1 min on both the intervention and control leg. This assessment of muscle function has been deemed valid and reliable
Timepoint [3] 370773 0
Baseline 4 hours 24 hours 48 hours 72 hours 96 hours
Secondary outcome [4] 370774 0
Range of Motion: Range of motion (ROM) at the hip joint will be assessed using a goniometer. A goniometer is a non-invasive standard device for measuring angles, Passive hip flexion and extension will be assessed on all participants using standardised protocols. Three trials for each movement will be recorded, and the median value used for analysis.
Timepoint [4] 370774 0
Baseline 4 hours 24 hours 48 hours 72 hours 96 hours
Secondary outcome [5] 370775 0
Inflammation: An anthropometric measuring tape will be used to measure mid-thigh circumference, the midpoint between the anthropometric sites trochanterion and tibiale laterale. Circumference measurements will be used as an indicator of acute changes in thigh volume likely to occur from osmotic fluid shifts or inflammation, which is often associated with muscle damage and eccentric exercise
Timepoint [5] 370775 0
Baseline 4 hours 24 hours 48 hours 72 hours 96 hours
Secondary outcome [6] 371035 0
Range of Motion: Range of motion (ROM) at the knee joints will be assessed using a goniometer. A goniometer is a non-invasive standard device for measuring angles, Passive knee flexion and extension will be assessed on all participants using standardised protocols. Three trials for each movement will be recorded, and the median value used for analysis.
Timepoint [6] 371035 0
4 hours 24 hours 48 hours 72 hours 96 hours

Eligibility
Key inclusion criteria
Participants recruited for this study will be:
1. Males aged between 18-35 years, who are physically active, but naive to eccentric contraction dominated movements.
2. Free from injuries or conditions that may make it unsafe to exercise (i.e. answers no to everything on the adult pre-exercise screening tool)
3. Agree to discontinue anti-inflammatory or analgesic medications (oral and topical) 3 days prior to starting the study (NSAIDs, Opioids or Steroids) or any complementary medicines with known anti-inflammatory properties, for example turmeric, glucosamine or high strength fish oils for the duration of the study.
4. Agree not to introduce any new personal care products such as physiotherapy, OTCs, topical or oral complementary medicine products, skin care, personal hygiene products during the study (due to investigation of adverse effects on skin, skin care and personal hygiene products is prohibited).
5. Agree to abstain for physical activity for up to 96 hours post eccentric exercise.
Minimum age
18 Years
Maximum age
35 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Participants will be excluded if they:
1. Regularly participate in strength training or long distance running (due to the eccentric contractions associated with these activities).
2. Allergy to CKPRO or any of its ingredients
3. Individuals with; broken or infected skin proximal or on the application site; skin affected by diabetes
4. Individuals who have participated in other clinical trials within 28 days prior starting of the study.
5. Individuals with medical conditions which anti-inflammatory or analgesic medications must be used.
6. Individuals who do not meet any of the inclusion criteria.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The randomisation schedule was prepared by a researcher not involved in the coordination of the study using a computer-generated blocked random sequence. The code will be kept by two independent researchers in a locked computer file. The preparations will be distributed in numerical order, matching the participants’ enrolment number with the number on the intervention label. Once the preparations
are labelled, they will be sent to a member of the research team working with the athletes, who will distribute the bottles to the participants. This member will be blinded to the preparation allocation. Opaque code break envelopes will be produced to deal with any serious adverse effects and kept by an independent party. The code will not be broken until the trial is completed and the database will be locked. The code will be broken in two steps, firstly allocation to group A or B to allow blinded statistical analysis, and secondly into actual treatment allocation on completion of the analysis. The statistician, study coordinator and the participants will be blinded to treatment allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
computer-generated blocked random sequence
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
A sample size calculation was performed by statistician AI Welvaert, who determined a total of 45 participants (accounting for a 10% drop out) will be required in this two-treatment (active and placebo) crossover study. The probability is 90 percent that the study will detect a treatment difference at a two-sided 0.05 significance level, if the true difference between treatments is 1.4 units on the VAS. This is based on the assumption that the standard deviation of the difference in the response variable is 2.6.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/07/2019
Actual
Date of last participant enrolment
Anticipated
30/10/2019
Actual
Date of last data collection
Anticipated
1/12/2019
Actual
Sample size
Target
45
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW

Funding & Sponsors
Funding source category [1] 302862 0
Commercial sector/Industry
Name [1] 302862 0
Fabrica De Medicina Chinesa Cheong Kun
Country [1] 302862 0
Macao
Primary sponsor type
University
Name
The University of Canberra
Address
Building 1/11 Kirinari St, Bruce ACT 2617.
Country
Australia
Secondary sponsor category [1] 302814 0
University
Name [1] 302814 0
The University of Sydney
Address [1] 302814 0
Level 3, Administration Building (F23), University of Sydney NSW 2006
Country [1] 302814 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303436 0
The University of Canberra Human Research Ethics Commitee
Ethics committee address [1] 303436 0
Ethics committee country [1] 303436 0
Australia
Date submitted for ethics approval [1] 303436 0
01/04/2019
Approval date [1] 303436 0
15/04/2019
Ethics approval number [1] 303436 0
1877

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

Contacts
Principal investigator
Name 93666 0
A/Prof Kate Pumpa
Address 93666 0
The University of Canberra, Building 1/11 Kirinari St, Bruce ACT 2617.
Country 93666 0
Australia
Phone 93666 0
+61 2 6201 2936
Fax 93666 0
Email 93666 0
[email protected]
Contact person for public queries
Name 93667 0
Joanna Harnett
Address 93667 0
School of Pharmacy The University of Sydney Science Rd, Camperdown Campus Sydney 2006
Country 93667 0
Australia
Phone 93667 0
+61 2 9351 7009
Fax 93667 0
Email 93667 0
[email protected]
Contact person for scientific queries
Name 93668 0
Joanna Harnett
Address 93668 0
School of Pharmacy The University of Sydney Science Rd, Camperdown Campus Sydney 2006
Country 93668 0
Australia
Phone 93668 0
+61 2 9351 7009
Fax 93668 0
Email 93668 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No
No IPD sharing reason/comment: To preserve the confidentiality of all participants. Raw data collected during this trial will be reported in publications (no personal identifying information)



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.