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Trial registered on ANZCTR


Registration number
ACTRN12621000603819
Ethics application status
Approved
Date submitted
16/03/2021
Date registered
20/05/2021
Date last updated
30/11/2023
Date data sharing statement initially provided
20/05/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Elevated sodium intake and muscle cramp
Scientific title
Effects increased daily sodium intake on mild electrical stimulation induced muscle cramp in healthy adults.
Secondary ID [1] 303688 0
None
Universal Trial Number (UTN)
U1111-1266-1200
Trial acronym
Linked study record
This is a sub-study linked to ACTRN12617000164392 currently on hold due to concerns with previously cramp induction models. The current sub-study aims to validate our improved mild-electrical stimulation protocol to induce muscle cramp within the Abductor Hallicus (DOI: 10.1088/1361-6579/ab8855). If this validation is successful then we will update registration details for ACTRN12617000164392 and proceed with the proposed study using our improved mild-electrical stimulation protocol.

Health condition
Health condition(s) or problem(s) studied:
Muscle Cramp 321091 0
Condition category
Condition code
Musculoskeletal 318893 318893 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will increase their daily sodium intake by 150 mmol per day for seven days. Sodium intake will be increase using slow sodium tablets. The participants will take a total of 15 tablets, each tablet contains 10 mmol of sodium. The participants will be asked to interspace these regularly throughout the day i.e. a tablet approximately every awake hour. They will be advised to consume 70 mL of water per tablet as per the product label, with no requirements around food intake.

Adherence will be assessed by verbal confirmation with each participant that they took the 15 tablets each day for seven days and they will be asked to return any remaining tablets. This the response and number of tablets remaining will be formally noted within the data collection sheets.

The investigators will be in regular contact with the participants to remind them of their appointments. A investigator is present at all appointments and formal recording of appointment attendance is taken. Participants will also be encouraged to be in regular contact with the investigators about adherence to the tablets and any symptoms they may feel.

Participants will attend clinical research rooms with the Department of Medicine, University of Otago, Dunedin hospital on five occasions. The first session is approximately 30 minutes to familiarise the participants to the measures and the mild-electrical stimulation protocol used to induce muscle cramp in the Abductor Hallucis muscle as with the attached published methodology study (DOI: 10.1088/1361-6579/ab8855). Following the familiarisation session the participants attend four experimental sessions, each approximately 1 hour long at the same time of day at baseline, days 2, 4 and 7 following increased daily sodium intake. The familiarisation session will occur within two weeks (usually a week) of the baseline session. The baseline session will occur within two days of the participants being required to commence taking the slow release sodium tablets.

Briefly an incremental graded 150-stimulus train is used to induce muscle cramp, with a maximum current of 80 milliamps at a maximum stimulation frequency of 70 hertz targeting the Abductor Hallucis muscle using a constant current stimulator (DS7R, Digitimer Ltd, England). The cathode (Ambu Bluesensor M, Denmark; area ~79 mm2) is placed over point of the main motor point for the Abductor hallucis (within an area defined by the anatomical landmark of the navicular tuberosity - up to 1.5 cm posterior and 2 cm inferior). The anode an 8 × 6 cm carbon electrode covered with conductive gel (Spectra 360 Electrode Gel, NJ, USA) is secured on the opposite side of the participant’s foot to the motor point search area. Superficial EMG recording electrodes (Ambu Bluesensor M, Denmark; area ~79 mm2) is placed over abductor hallucis muscle belly anteriorly to the motor point; the positive electrode was placed posteriorly to the first metatarsophalangeal joint and the negative electrode was placed between the positive electrode and the anterior edge of the search area for abductor hallucis motor point. The participants leg and foot were placed within a turnbuckle ankle orthosis (product reference number: 66 426, AliMed Inc. Dedham, MA, USA) set to comfortably and consistently support and hold the ankle in plantarflexion and foot in inversion.

The electrical stimulation will be administered by the investigators. Whilst continuously measuring electromyograph activity and electrocardiogram (via a standard limb lead II configuration) through Labchart 8 software and a Powerlab (3508/P) analogue-to-digital converter sampling at 10,000 Hz (ADInstruments, Dunedin, NZ), and intermittently measuring non-invasive brachial blood pressure (Connex ProBP 3400 series Welch Allyn).
Intervention code [1] 319984 0
Treatment: Other
Comparator / control treatment
The study does not have a specific comparator/control treatment.

The participants act as their own controls with the repeated measures design of this project. Muscle cramp is induced with mild-electrical stimulation at baseline, then at 2, 4, and 7 days of increasing their dialy sodium intake by 150 mmol using slow release sodium tablets.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 326834 0
Muscle cramp threshold in Hertz (Hz).

This will be assessed by continuously measuring the electromyography activity prior to, during and following the mild-electrical stimulation. The presence of muscle cramp following stimulation is determined by exceeding a threshold of electromyography activity mean plus two times the standard deviation prior to the mild-electrical stimulation for at least 100 milliseconds. Participants are asked to relax and allow for the muscle cramp to self-resolve. The muscle cramp is self-resolved when the electromyography activity has drop below the detailed threshold above for at least 100 milliseconds.

The stimulation frequency at which muscle cramp is present is noted and then refined using the documented approach in methods study (DOI: 10.1088/1361-6579/ab8855) to triplicate muscle cramp following mild-electrical stimulation.

The stimulation frequency at which the three muscle cramps occur is averaged and taken as the muscle cramp threshold for each participant.
Timepoint [1] 326834 0
Will be assessed at baseline prior to and following increasing daily sodium intake with slow release sodium tablets® for 7 days.

This primary outcome measure along with primary outcomes 2 and 3 will be used to inform the effects of 7 days of increasing daily sodium intake by 150 mmol/day using slow release sodium tablets®.
Primary outcome [2] 327244 0
Mean muscle cramp amplitude in millivolts (mV).

This will be assessed by continuously measuring the electromyography activity prior to, during and following the mild-electrical stimulation. The presence of muscle cramp following stimulation is determined by exceeding a threshold of electromyography activity mean plus two times the standard deviation prior to the mild-electrical stimulation for at least 100 milliseconds. Participants are asked to relax and allow for the muscle cramp to self-resolve. The muscle cramp is self-resolved when the electromyography activity has drop below the detailed threshold above for at least 100 milliseconds.

The stimulation frequency at which muscle cramp is present is noted and then refined using the documented approach in methods study (DOI: 10.1088/1361-6579/ab8855) to triplicate muscle cramp following mild-electrical stimulation.

The mean muscle cramp amplitude calculated by averaging the three muscle cramps used to define the muscle cramp threshold (see primary outcome 1) for each participant. The muscle cramp amplitude is derived from the area under the curve of the electromyograph signal when muscle cramp is present as detailed with the criteria above.
Timepoint [2] 327244 0
Will be assessed at baseline prior to and following increasing daily sodium intake with slow release sodium tablets® 7 for days.

This primary outcome measure along with primary outcomes 1 and 3 will be used to inform the effects of 7 days of increasing daily sodium intake by 150 mmol/day using slow release sodium tablets®.
Primary outcome [3] 327245 0
Mean muscle cramp duration in seconds (s).

This will be assessed by continuously measuring the electromyography activity prior to, during and following the mild-electrical stimulation. The presence of muscle cramp following stimulation is determined by exceeding a threshold of electromyography activity mean plus two times the standard deviation prior to the mild-electrical stimulation for at least 100 milliseconds. Participants are asked to relax and allow for the muscle cramp to self-resolve. The muscle cramp is self-resolved when the electromyography activity has drop below the detailed threshold above for at least 100 milliseconds.

The stimulation frequency at which muscle cramp is present is noted and then refined using the documented approach in methods study (DOI: 10.1088/1361-6579/ab8855) to triplicate muscle cramp following mild-electrical stimulation.

The mean muscle cramp duration calculated by averaging the three muscle cramps used to define the muscle cramp threshold (see primary outcome 1) for each participant. The muscle cramp duration is measured when muscle cramp is present as detailed with the criteria above.
Timepoint [3] 327245 0
Will be assessed at baseline prior to and following increasing daily sodium intake with slow release sodium tablets® for 7 days.

This primary outcome measure along with primary outcomes 1 and 2 will be used to inform the effects of 7 days of increasing daily sodium intake by 150 mmol/day using slow release sodium tablets®.
Secondary outcome [1] 392837 0
Muscle cramp threshold in Hertz (Hz) time course of change.

This will be assessed by continuously measuring the electromyography activity prior to, during and following the mild-electrical stimulation. The presence of muscle cramp following stimulation is determined by exceeding a threshold of electromyography activity mean plus two times the standard deviation prior to the mild-electrical stimulation for at least 100 milliseconds. Participants are asked to relax and allow for the muscle cramp to self-resolve. The muscle cramp is self-resolved when the electromyography activity has drop below the detailed threshold above for at least 100 milliseconds.

The stimulation frequency at which muscle cramp is present is noted and then refined using the documented approach in methods study (DOI: 10.1088/1361-6579/ab8855) to triplicate muscle cramp following mild-electrical stimulation.

The stimulation frequency at which the three muscle cramps occur is averaged and taken as the muscle cramp threshold for each participant.
Timepoint [1] 392837 0
Will be assessed at baseline prior to and following 2, 4 and 7 days of increasing daily sodium intake with slow release sodium tablets® for 7 days.

This secondary outcome measure along with secondary outcomes 2 and 3 will be used to inform the time course of change caused by 7 days of increasing daily sodium intake by 150 mmol/day using slow release sodium tablets®.
Secondary outcome [2] 394346 0
Mean muscle cramp amplitude in millivolts (mV) time course of change.

This will be assessed by continuously measuring the electromyography activity prior to, during and following the mild-electrical stimulation. The presence of muscle cramp following stimulation is determined by exceeding a threshold of electromyography activity mean plus two times the standard deviation prior to the mild-electrical stimulation for at least 100 milliseconds. Participants are asked to relax and allow for the muscle cramp to self-resolve. The muscle cramp is self-resolved when the electromyography activity has drop below the detailed threshold above for at least 100 milliseconds.

The stimulation frequency at which muscle cramp is present is noted and then refined using the documented approach in methods study (DOI: 10.1088/1361-6579/ab8855) to triplicate muscle cramp following mild-electrical stimulation.

The mean muscle cramp amplitude calculated by averaging the three muscle cramps used to define the muscle cramp threshold (see primary outcome 1) for each participant. The muscle cramp amplitude is derived from the area under the curve of the electromyograph signal when muscle cramp is present as detailed with the criteria above.
Timepoint [2] 394346 0
Will be assessed at baseline prior to and following 2, 4 and 7 days of increasing daily sodium intake with slow release sodium tablets® for 7 days.

This secondary outcome measure along with secondary outcomes 1 and 3 will be used to inform the time course of change caused by 7 days of increasing daily sodium intake by 150 mmol/day using slow release sodium tablets®.
Secondary outcome [3] 394347 0
Mean muscle cramp duration in seconds (s) time course of change.

This will be assessed by continuously measuring the electromyography activity prior to, during and following the mild-electrical stimulation. The presence of muscle cramp following stimulation is determined by exceeding a threshold of electromyography activity mean plus two times the standard deviation prior to the mild-electrical stimulation for at least 100 milliseconds. Participants are asked to relax and allow for the muscle cramp to self-resolve. The muscle cramp is self-resolved when the electromyography activity has drop below the detailed threshold above for at least 100 milliseconds.

The stimulation frequency at which muscle cramp is present is noted and then refined using the documented approach in methods study (DOI: 10.1088/1361-6579/ab8855) to triplicate muscle cramp following mild-electrical stimulation.

The mean muscle cramp duration calculated by averaging the three muscle cramps used to define the muscle cramp threshold (see primary outcome 1) for each participant. The muscle cramp duration is measured when muscle cramp is present as detailed with the criteria above.
Timepoint [3] 394347 0
Will be assessed at baseline prior to and following 2, 4 and 7 days of increasing daily sodium intake with slow release sodium tablets® for 7 days.

This secondary outcome measure along with secondary outcomes 1 and 2 will be used to inform the time course of change caused by 7 days of increasing daily sodium intake by 150 mmol/day using slow release sodium tablets®.

Eligibility
Key inclusion criteria
Able to give informed consent; Absence of pre-hypertension or hypertension (defined as a systolic blood pressure >130 mm Hg and a diastolic blood pressure >85 mm Hg or current treatment with antihypertensive therapy); age between 18 and 70 years; non-smoker; body mass index <30 (kg/m2); and no history of cardiovascular disease, diabetes or renal disease.
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
History of peripheral neuropathy (damaged nerves in the feet and/or hands), underlying primary muscle disorder, cardiovascular disease, diabetes, renal disease or acutely unwell.

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/12/2023
Actual
Date of last participant enrolment
Anticipated
1/12/2024
Actual
Date of last data collection
Anticipated
1/10/2024
Actual
Sample size
Target
5
Accrual to date
Final
Recruitment outside Australia
Country [1] 23536 0
New Zealand
State/province [1] 23536 0
Otago

Funding & Sponsors
Funding source category [1] 308105 0
University
Name [1] 308105 0
University of Otago
Country [1] 308105 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Address
University of Otago
PO Box 56
Dunedin 9054
Country
New Zealand
Secondary sponsor category [1] 308855 0
None
Name [1] 308855 0
Address [1] 308855 0
Country [1] 308855 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308091 0
Southern Health and Disabilities Ethics Committees
Ethics committee address [1] 308091 0
Ethics committee country [1] 308091 0
New Zealand
Date submitted for ethics approval [1] 308091 0
20/04/2021
Approval date [1] 308091 0
28/07/2023
Ethics approval number [1] 308091 0
2023 AM 6022

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

Contacts
Principal investigator
Name 109502 0
Prof Rob Walker
Address 109502 0
Department of Medicine Dunedin School of Medicine University of Otago PO Box 56 Dunedin 9054
Country 109502 0
New Zealand
Phone 109502 0
+64 274359552
Fax 109502 0
Email 109502 0
rob.walker@otago.ac.nz
Contact person for public queries
Name 109503 0
Luke Wilson
Address 109503 0
Department of Medicine Dunedin School of Medicine University of Otago PO Box 56 Dunedin 9054
Country 109503 0
New Zealand
Phone 109503 0
+64 274491401
Fax 109503 0
Email 109503 0
luke.wilson@otago.ac.nz
Contact person for scientific queries
Name 109504 0
Luke Wilson
Address 109504 0
Department of Medicine Dunedin School of Medicine University of Otago PO Box 56 Dunedin 9054
Country 109504 0
New Zealand
Phone 109504 0
+64 274491401
Fax 109504 0
Email 109504 0
luke.wilson@otago.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All data de-identified will be available to those who provide a reasonable request to the corresponding author of published work or the contact person for scientific queries.
When will data be available (start and end dates)?
The data will be avaliable following publication likely early 2022 for a period of at least 10 years.
Available to whom?
To those who make a reasonable request to the corresponding author of published work or the contact person for scientific queries.
Available for what types of analyses?
This will be discussed with those making a reasonable request to the corresponding author of published work or the contact person for scientific queries.
How or where can data be obtained?
From the corresponding author of published work or the contact person for scientific queries. Email is the preferred method of contact. luke.wilson@otago.ac.nz.


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.