Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617001610325
Ethics application status
Approved
Date submitted
17/11/2017
Date registered
7/12/2017
Date last updated
1/11/2019
Date data sharing statement initially provided
23/11/2018
Date results information initially provided
1/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating the effects of Gynostemma pentaphyllum supplementation on muscle in Males
Scientific title
Investigating the effects of Gynostemma pentaphyllum supplementation on muscle in Males
Secondary ID [1] 293379 0
None
Universal Trial Number (UTN)
U1111-1205-2680
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Overweight/obesity 305514 0
Muscle function 305515 0
Condition category
Condition code
Alternative and Complementary Medicine 304757 304757 0 0
Herbal remedies
Diet and Nutrition 304758 304758 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The investigational product is a commercially available capsule-form herbal medicine containing Gynostemma pentaphyllum (G. pentaphyllum) extract (ActivAMP). The daily dose will be 450mg across 2 capsules daily.
The aim of this study is to examine the effect of supplementation with G. pentaphyllum for 4 weeks on muscle AMPK activity. Since AMPK is involved in energy supply and performance, and its activity is also altered following exercise, participants following supplementation will undertake aerobic exercise performance trials. Muscle samples will be collected by a Trained Medical Doctor at different times during the steady state exercise to allow measurement of changes in AMPK activity during exercise. As AMPK also alters glucose uptake in muscle, we will also measure glucose uptake by the muscle. Blood and muscle samples will be collected following the supplementation period.

The effects of the supplementation or placebo on aerobic exercise performance using two different measures including a steady state and time to fatigue test (TtE) and a 20km time trial using a double blind randomised cross-over study design will be undertaken. Participants will undertake a graded exercise test (GXT) to determine their maximal aerobic exercise capacity, which will be used to set the exercise intensities for the steady state submaximal exercise (SS) and TtE tests. They will then undertake a familiarisation of the TtE and TT within a week of the GXT. Two weeks following the familiarisation testing the participants will start supplementing with either placebo or the supplement (randomised and double blinded) for 28 days and then undertake the SS+TtE followed by the TT separated by two days (thus 30 days supplementation). The participant will then have a four week washout period before repeating the supplementation and exercise testing regimen with the treatment not used in the first trial. The measures to assess the endurance exercise performance are time to complete the TT, work done and power outputs in the TT, while time to fatigue will be determined during the TtE. All exercise completed on a stationary bike.

Supplementation
2 weeks after the familiarisation TT participants will be provided with 60 capsules of either placebo or the active supplement. They will be asked to consume 2 capsules each day with their morning meal. Adherence monitored via capsule return.
Dietary intake will be fully controlled (all foods provided) 3 days prior to the initial GXT for the week prior to each SS+TtE through to after the TT test. Energy requirements for each participant will be estimated using the Harris Benedict equation and adjusted for physical activity level such that an energy balanced diet is consumed that meets the Australian guide to Healthy Eating. Diets will be designed by a qualified dietitian.
Activity will be monitored throughout the intervention to ensure a standardisation of overall activity levels via the use of accelerometers at baseline and during weeks 1 and 4 of the interventions for a one week period.

SS+TtE: Participants will undertake 60 min of SS exercise on a stationary bike, after which they will have 5 min of active recovery (30 W) and then perform the TtE test which will be completed at a power output of 50% between that of the ventilatory threshold and the VO2 peak until voluntary exhaustion.
Muscle: Muscle biopsies will be taken at rest, 30mins into the SS exercise and at the conclusion of the 60 min SS test (6 biopsies per person) by a trained medical professional. Muscle samples will be measured by the Oxygraph O2k high-resolution respirometer (Oroboros Instruments, Innsbruck, Austria) via a substrate, uncoupler, inhibitor titration (SUIT) protocol. Frozen muscle samples will be used for the determination of AMPK activity, gene expression and protein abundance of key metabolic pathways.

Tracer infusion on SS+TtE day: The glucose tracer will commence 30 minutes after the resting biopsy has been taken. Syringe pumps will be used to infuse the [6,6-2H]-glucose. The solution will be infused at 0.2 ml.min-1(12 ml.hr-1). A bolus dose of glucose tracer (54 µmol.kg-1) will be given via the catheter prior to the initiation of the continuous constant infusion (0.62 µmol.kg-1.min-1) which will commence two hours prior to exercise and cease upon completion of exercise.
Blood sampling: Blood will be collected prior to exercise and during the SS exercise tests for standard markers of metabolism and glucose tracer analysis and at start and conclusion of TtE test. Resting samples will also be collected for subsequent analysis (basic subject characteristics (glucose, cholesterol, triglycerides etc) as well as potentially other markers of metabolism and AMPK signalling (ie. leptin, adiponectin etc).

Two days following the SS+TtE day, participants will, after an overnight fast, undertake a 20 km TT on a velotron™ cycle ergometer. Following this 20 km TT participants will undertake a 4 week washout period.
Intervention code [1] 299636 0
Treatment: Other
Comparator / control treatment
The placebo is taken twice daily - maltodextrin vegetarian capsule
Control group
Placebo

Outcomes
Primary outcome [1] 303984 0
The composite primary outcome of AMPK activity and signalling (determined via direct muscle activity assay and gene and protein expression)
Timepoint [1] 303984 0
Following 4 weeks of supplementation
Secondary outcome [1] 340632 0
Exercise performance as determined by the combination of Time to Exhaustion and 20km time trial performance on the stationary bike
Timepoint [1] 340632 0
Following 4 weeks of supplementation
Secondary outcome [2] 340633 0
glucose handling as determined by nonradioactive glucose tracer removal
Timepoint [2] 340633 0
Following 4 weeks of supplementation
Secondary outcome [3] 340894 0
mitochondrial function assessed for electron transport system respiration, oxidative phosphorylation, and hydrogen peroxide (H2O2) emission measured by the Oxygraph O2k high-resolution respirometer (Oroboros Instruments, Innsbruck, Austria) via a substrate, uncoupler, inhibitor titration (SUIT) protocol.
Timepoint [3] 340894 0
Following 4 weeks of supplementation
Secondary outcome [4] 340895 0
Plasma adiponectin as determined by ELISA technique
Timepoint [4] 340895 0
Following 4 weeks of supplementation
Secondary outcome [5] 340896 0
Plasma leptin as determined by ELISA technique.
Timepoint [5] 340896 0
Following 4 weeks of supplementation

Eligibility
Key inclusion criteria
• Male aged between 18 and 35 years.
• Have a BMI less than 25 kg/m2
• Are not currently taking blood pressure, lipid lowering or insulin sensitising medications.
• Are not taking vitamins or natural supplements or have not taken these supplements for 1 month prior to this study
Minimum age
18 Years
Maximum age
35 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Individuals with known cardiovascular or respiratory conditions (e.g. asthma, cardiac arrhythmias), hypertension (resting blood pressure >145/95), bleeding disorders, eating disorders, skin or anaesthetic allergies, musculoskeletal injuries that may be aggravated by the exercise protocol, type 1 or 2 diabetes, or current medication including; antihypertensives, insulin sensitisers, antiobesity drugs and steroidal medications

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)
A researcher not directly involved in the analysis of the study results will prepare the randomisation schedule using block randomisation to maintain balance between treatment arms
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be sequentially numbered, details of supplements will not be informed to researchers.
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
Physiological measures include ventilatory and gas exchange variables as well as performance measures, we will use paired t test and two-way repeated measures ANOVA for data analysis.
Blood and muscle sample analyses will be performed using paired t test and two-way
repeated measures ANOVA.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
8/01/2018
Actual
1/08/2018
Date of last participant enrolment
Anticipated
28/02/2019
Actual
28/06/2019
Date of last data collection
Anticipated
30/08/2019
Actual
30/08/2019
Sample size
Target
19
Accrual to date
Final
15
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 298005 0
Commercial sector/Industry
Name [1] 298005 0
Gencor Pacific
Country [1] 298005 0
Hong Kong
Primary sponsor type
University
Name
Victoria University
Address
PO Box 14428
Melbourne Vic 8001
Country
Australia
Secondary sponsor category [1] 297082 0
None
Name [1] 297082 0
Address [1] 297082 0
Country [1] 297082 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299041 0
Victoria University Human Research Ethics Committee
Ethics committee address [1] 299041 0
PO Box 14428
Melbourne Vic 8001
Ethics committee country [1] 299041 0
Australia
Date submitted for ethics approval [1] 299041 0
31/10/2017
Approval date [1] 299041 0
08/12/2017
Ethics approval number [1] 299041 0
Application ID: HRE17-151

Summary
Brief summary
Gynostemma pentaphyllum (G. pentaphyllum) is a plant species originating in Asia. Animal and human studies have shown that extracts from the leaf of this plant can decrease fat mass. Evidence from cell culture studies indicates that the decrease of fat mass is mediated via the AMP Kinase (AMPK) signalling pathway, a key pathway involved in both energy supply and performance of muscle. However, it is still unknown whether the supplement of this extract in humans influences the AMPK pathway.
Therefore, the aim of this study is to examine the effect of supplementation with a dried leaf extract of G. pentaphyllum for 4 weeks on muscle AMPK activity. Since AMPK is involved in energy supply and performance, and its activity is also altered following exercise, participants following supplementation will undertake aerobic exercise performance tests using two different measures: a combined steady state and time to fatigue test (TtE) and a 20km time trial. Muscle samples will be collected at different times during the steady state exercise to allow measurement of changes in AMPK activity during exercise, while the TtE and the 20km time trial will provide markers of performance. As AMPK also alters glucose uptake in muscle, we will also measure glucose uptake by the muscle. Blood and muscle samples will be collected by an experienced medical doctor following the supplementation period.
This study will help to identify whether the leaf extract alters AMPK activity in muscle, which will determine if the extract would be beneficial for improving exercise performance as well as metabolic diseases such as obesity and diabetes.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 79086 0
Prof Andrew McAinch
Address 79086 0
College of Health and Biomedicine,
Victoria University
PO Box 14428
Melbourne Vic 8001
Country 79086 0
Australia
Phone 79086 0
+61 3 9919 2019
Fax 79086 0
Email 79086 0
[email protected]
Contact person for public queries
Name 79087 0
Prof Andrew McAinch
Address 79087 0
College of Health and Biomedicine,
Victoria University
PO Box 14428
Melbourne Vic 8001
Country 79087 0
Australia
Phone 79087 0
+61 3 9919 2019
Fax 79087 0
Email 79087 0
[email protected]
Contact person for scientific queries
Name 79088 0
Prof Andrew McAinch
Address 79088 0
College of Health and Biomedicine,
Victoria University
PO Box 14428
Melbourne Vic 8001
Country 79088 0
Australia
Phone 79088 0
+61 3 9919 2019
Fax 79088 0
Email 79088 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
Will need to discuss with ethics committee about what we can and can not share based on our consent.


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
SourceTitleYear of PublicationDOI
Dimensions AIGynostemma Pentaphyllum Increases Exercise Performance and Alters Mitochondrial Respiration and AMPK in Healthy Males2023https://doi.org/10.3390/nu15224721
N.B. These documents automatically identified may not have been verified by the study sponsor.