Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000519651
Ethics application status
Approved
Date submitted
24/04/2023
Date registered
19/05/2023
Date last updated
4/08/2023
Date data sharing statement initially provided
19/05/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
The pharmacokinetics and dose response to ingestion of liposomal encapsulated creatine monohydrate in adults
Scientific title
The pharmacokinetics and dose response to ingestion of liposomal encapsulated creatine monohydrate in adults
Secondary ID [1] 309483 0
None
Universal Trial Number (UTN)
Trial acronym
LipoCre
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sporting Performance 329754 0
Condition category
Condition code
Diet and Nutrition 326650 326650 0 0
Other diet and nutrition disorders
Musculoskeletal 326803 326803 0 0
Normal musculoskeletal and cartilage development and function

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study design will be a double-blind, randomised, crossover comprising six arms in a clinical laboratory setting. This will involve baseline measures plus six visits to the laboratory per participant. Three testing sessions/arms will use the product being tested - liposomal creatine - at different doseages, the remaining three sessions will use creatine monohydrate at equimolar doseages as control. Liposomal creatine consists of creatine monohydrate encapsulated in liposomal components (phosphatidylcholine). Samples will be provided orally, dissolved in water with maltodextrin. Each dose will be given as 300ml of artificially flavoured and coloured water with 1, 2.5, and 5g, respectively.

Each session will include:

Baseline:
Online screening to complete health questionnaire and informed consent. Baseline parameters (personal data, history, anthropometric measures) will be recorded. Instructions and a container for the first baseline 24h urine collection will be provided. Baseline urine will be collected for 24h before each visit.

Visit 1:
Takes place at least 24-h after baseline session. Completion of the first arm of the test protocol.
- Participants will report to the laboratory after overnight fast between 6-900h.
- Recovery of the 24-h urine.
- Subsequent 24-h urine collection will start on the onset of the supplement protocol.
- Their non-dominant or hand of choice will be placed in the heat-hand box and warmed for 20-30 min. A 21-23 GA catheter will be placed retrograde (or anterograde as distal as possible if difficulty) in a dorsal hand vein for blood sampling and the line kept patent with slow rate (0.5-1.0 ml/min) saline drip infusion.
- Blood will be collected at time=0 (prior to Creatine supplement ingestion), and at the following time periods after: 0, 10, 20, 30, 40, 50, 60, 90, 120, 180, 240, 300 min.
- After baseline blood sample is taken, participants will be given a pre-mixed solution containing the supplement, and supervised by the researcher as they consume it in as short a time as possible.
- At baseline and every 30 min a gastrointestinal comfort scale will be completed by the participants.

Visits 2-6:
Will be separated by at least 7 days washout and will be repeats of visit 1 but with a different test supplement. The test supplement will be provided in randomized order presentation.
Intervention code [1] 325912 0
Treatment: Other
Comparator / control treatment
The control conditions will be three sessions with equimolar doses (1, 2.5, and 5g in 300ml) of creatine monohydrate dissolved in 300ml water, artifically coloured and flavoured.
Control group
Active

Outcomes
Primary outcome [1] 334517 0
The primary outcome of the study is the total area under the plasma creatine - time curve.
Timepoint [1] 334517 0
Per testing session:
Blood samples will be collected at time=0 (prior to Cr supplement ingestion), and at the following time periods after: 0, 10, 20, 30, 40, 50, 60, 90, 120, 180, 240, 300 min post-ingestion
Secondary outcome [1] 420979 0
Gut comfort response measured on a gastrointestinal comfort scale.
Timepoint [1] 420979 0
At baseline and every 30min after ingestion for up to 6 hours post-ingestion
Secondary outcome [2] 420980 0
Slope to peak plasma creatine concentration (plotted against time).
Timepoint [2] 420980 0
Blood samples collected at time=0 (prior to Cr supplement ingestion), and at the following time periods after: 0, 10, 20, 30, 40, 50, 60, 90, 120, 180, 240, 300 min post-ingestion
Secondary outcome [3] 420981 0
Peak plasma creatine concentration.
Timepoint [3] 420981 0
Blood samples collected at time=0 (prior to Cr supplement ingestion), and at the following time periods after: 0, 10, 20, 30, 40, 50, 60, 90, 120, 180, 240, 300 min post-ingestion
Secondary outcome [4] 420982 0
Time to peak creatine concentration.
Timepoint [4] 420982 0
Blood samples collected at time=0 (prior to Cr supplement ingestion), and at the following time periods after: 0, 10, 20, 30, 40, 50, 60, 90, 120, 180, 240, 300 min post-ingestion
Secondary outcome [5] 420983 0
24h urinary total creatine.
Timepoint [5] 420983 0
Baseline 24h urine collection will occur in the 24h prior to every testing session.
Subsequent 24h urine collection will occur starting at the onset of each supplement protocol.

Eligibility
Key inclusion criteria
Adults aged 18-45 with BMI between 18-30. Participants will be required to pass a Health Screen Questionnaire.
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Failure to meet health requirements defined in the Health Questionnaire
• Known bleeding disorder or blood borne disease
• Gastrointestinal (e.g., cancer, celiac, irritable bowel) or metabolic (e.g., diabetes, hyperthyroid) disease
• Taking medications thought to interfere with the study outcomes
• Currently participating or having participated in another clinical study during the last four weeks prior to the beginning of this study that may affect results
• Habitual creatine user or planning on starting supplementation during course of the study
• Recent change in high dietary creatine-containing food (meat, fish) intake or plan to change dietary pattern during participation in the study
• Oligomenorrhea or amenorrhea in women
• Currently on hormonal contraceptives including hormonal contracetive pills, hormonal IUD (including Mirena and Jaydess), hormonal injection (such as Depo Provera), or hormonal implant (such as rods)
• Unable to meet study requirements

Women will be asked to book testing sessions between days 3-8 of their cycle.

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)
Products will be in plain packaging, with unique coding to differentiate samples.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Latin square design will be used to allocate sequence for 6 treatments.
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
Pharmacokinetics
Statistical methods / analysis
All statistical analyses will be conducted using SAS. All Creatine parameters will be analyzed by a mixed-model. Fixed effects are product (liposomal creatine, creatine monohydrate), dose (1, 2.5, 5 g), order of treatment (=period), sequence (randomization block) and baseline value as a covariate. Random effect structure will be random product/subject=subjectid Type = UN and Repeated product/subject=subject subjectid*period Type=UN. Distributional assumptions will be checked by residuals over fitted values and qq-plots.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
7/08/2023
Actual
Date of last participant enrolment
Anticipated
27/10/2023
Actual
Date of last data collection
Anticipated
26/01/2024
Actual
Sample size
Target
12
Accrual to date
Final
Recruitment outside Australia
Country [1] 25406 0
New Zealand
State/province [1] 25406 0
Auckland

Funding & Sponsors
Funding source category [1] 313678 0
Commercial sector/Industry
Name [1] 313678 0
Pharmako Biotechnologies Pty Ltd.
Country [1] 313678 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Pharmako Biotechnologies Pty Ltd.
Address
Factory 2 & 3/ 2 Aquatic Drive.
Frenchs Forest,
NSW, 2086.
AUSTRALIA
Country
Australia
Secondary sponsor category [1] 315496 0
None
Name [1] 315496 0
Address [1] 315496 0
Country [1] 315496 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312843 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 312843 0
Postal address:
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140

Street address:
133 Molesworth Street
Thorndon
Wellington 6011
Ethics committee country [1] 312843 0
New Zealand
Date submitted for ethics approval [1] 312843 0
31/05/2023
Approval date [1] 312843 0
17/07/2023
Ethics approval number [1] 312843 0
18021

Summary
Brief summary
The purpose of the LipoCre study is to investigate the digestibility and bioavailability of liposomal creatine. Creatine is used as a sports supplement and in some other applications. Creatine is a naturally occurring compound found in foods like fish and meat that provides energy for rapid, powerful short burst maximal efforts in sports. The most common form of creatine used in supplements is creatine monohydrate (CrM), which can enhance high-intensity performance and training adaptations in various sports. CrM supplementation may also have potential benefits for brain health and function in tasks requiring memory and performing challenging tasks, diabetes, immunity, vascular and heart health, cancer, post-viral fatigue, and exercise capacity in children with muscular dystrophy.

However, one of the reported side-effects of 5 g doses of CrM is gut discomfort for an hour or two after ingestion. To address this issue, a recent innovation has been to wrap up CrM into liposomal vesicles, which are small lipid packages, to increase and speed absorption by the gut. The LipoCre study aims to investigate whether liposomal creatine provides greater benefits to delivery of creatine into the body, compared to creatine monohydrate, which may lead to further research into possible benefits for sports performance and some aspects of health.

The design is a 6-arm randomized crossover conducted in 12 adults aged 18 to 65 y.

In each arm of the study, the absorption kinetics of 3 doses of LCr (1, 2.5, and 5 g) will be compared to the same 3 doses of CrM. The identity of each treatment will be hidden to both the participants and researchers, with the code held by a third party.

In total, participants will come to the lab 7 times: 1 for introduction and 6 times for each arm of the study, representing the test day. In addition, they will collect all urine for the 24h prior to the test day, overnight, during, and again overnight up to the morning upon waking the day following.

Testing will consist of blood being collected from a hand-vein at regular intervals for 5.5 hours after creatine ingestion. Additionally, gut comfort will be measured at regular intervals on a linear scale. Participants will remain rested either fully or semi reclined on a research bed or chair during sampling and may do (1-handed) computer work, watch TV or relax.

Blood plasma be stored and later analyzed for Cr concentration using mass spectrometry at Massey University. Data will be analyzed to determine how much of and how fast the Cr has been absorbed. Results will be used to inform upon the dose strategy to be applied to studies on muscle and performance and possibly brain and cognitive function with the LCr product.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 126114 0
Prof David Rowlands
Address 126114 0
School of Sport, Exercise and Nutrition
Massey University East Precinct Albany Expressway, SH17
Albany, Auckland 0632
Country 126114 0
New Zealand
Phone 126114 0
+64 9 2136616
Fax 126114 0
Email 126114 0
[email protected]
Contact person for public queries
Name 126115 0
Prof David Rowlands
Address 126115 0
School of Sport, Exercise and Nutrition
Massey University East Precinct Albany Expressway, SH17
Albany, Auckland 0632
Country 126115 0
New Zealand
Phone 126115 0
+64 9 2136616
Fax 126115 0
Email 126115 0
[email protected]
Contact person for scientific queries
Name 126116 0
Prof David Rowlands
Address 126116 0
School of Sport, Exercise and Nutrition
Massey University East Precinct Albany Expressway, SH17
Albany, Auckland 0632
Country 126116 0
New Zealand
Phone 126116 0
+64 9 2136616
Fax 126116 0
Email 126116 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
Study data will be collected in non-identifiable form. Screening information and consent forms will have identifiable data. Only Miss Anja Zoellner and Dr David Rowlands will have access to identifiable data. No IPD will be shared due to participant privacy and confidentiality purposes.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
18939Study protocol  [email protected]
18940Informed consent form  [email protected]
18941Ethical approval  [email protected]
18942OtherAdvertisement [email protected] Advertisement 385764-(Uploaded-18-05-2023-13-44-34)-Study-related document.pdf
19086OtherData Management [email protected] Data Management
19087OtherParticipant Information Sheet [email protected] Participant Information Sheet



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

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No additional documents have been identified.