Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001444774
Ethics application status
Approved
Date submitted
7/11/2022
Date registered
11/11/2022
Date last updated
7/04/2024
Date data sharing statement initially provided
11/11/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of potassium bicarbonate supplementation on muscle protein synthesis in older women
Scientific title
Effect of potassium bicarbonate supplementation on myofibrillar protein synthesis in older women
Secondary ID [1] 308260 0
None
Universal Trial Number (UTN)
Trial acronym
Nutri-Age
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sarcopenia 328041 0
Osteoporosis 328042 0
Condition category
Condition code
Musculoskeletal 325098 325098 0 0
Other muscular and skeletal disorders
Musculoskeletal 325099 325099 0 0
Osteoporosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will consume a potassium bicarbonate nutritional supplement at a dose of 1.5 mmol/kg body mass/day, split into three separate doses consumed with meals, for 21 days. The potassium bicarbonate will be administered via oral capsules. The supplementation dose will be increased gradually over the first 3 days to minimise the risk of gastrointestinal disturbances. On day 1, participants will consume 0.5 mmol/kg body mass (split into two separate doses), 1 mmol/kg body mass on day 2 (split into three separate doses), and 1.5 mmol/kg body mass (split into three separate doses) from day 3 onwards.

Adherence will be monitored via the pill count tracking method. Each week participants will be provided with more capsules than required and asked to return any capsules not taken. The number of returned capsules will then be cross referenced against the number prescribed. Participants will be informed about the pill count tracking method to encourage them to comply.

This is a crossover trial and there will be a 21-day wash-out period between the active (potassium bicarbonate) and placebo treatments. The order of treatment will be randomised.
Intervention code [1] 324718 0
Prevention
Comparator / control treatment
The placebo will consist of microcrystalline cellulose and will be provided in capsules that are appearance- and taste-matched to the potassium bicarbonate.
Control group
Placebo

Outcomes
Primary outcome [1] 332918 0
Daily myofibrillar protein synthesis (MyoPS) rates will be measured via oral deuterated water (D2O) administration combined with skeletal muscle biopsy sampling
Timepoint [1] 332918 0
MyoPS will be measured over the final 7-days of the two 21-day phases (i.e. potassium bicarbonate and placebo) of this crossover trial. On day 13 of each phase, participants will consume a 400 mL loading dose of D2O in eight doses at 1.5 h intervals. From days 14-20 of each phase, participants will consume single daily 50 mL top-up D2O doses.
Secondary outcome [1] 415101 0
Serum N-terminal propeptide of type I procollagen (PINP), a marker of bone formation, measured using ELISA kits.
Timepoint [1] 415101 0
Pre- and post- each 21-day phase.
Secondary outcome [2] 415102 0
Serum C-terminal telopeptide of type I collagen (CTX-I), a measure of bone resorption, measured using ELISA kits.
Timepoint [2] 415102 0
Pre- and post- each 21-day phase.
Secondary outcome [3] 415103 0
24-h urine pH will be measured using a standard pH meter.
Timepoint [3] 415103 0
At screening, pre- and post- each 21-day phase
Secondary outcome [4] 415108 0
Dietary intake will be assessed via a 3-day food record
Timepoint [4] 415108 0
Pre- and post- each 21-day phase
Secondary outcome [5] 415139 0
Serum potassium concentration will be measured via indirect ISE (Ion Selective Electrode) measurement compensated kinetic Jaffe method, with IDMS-traceable calibration
Timepoint [5] 415139 0
Screening, and on day 13 of each 21-day phase
Secondary outcome [6] 415140 0
24-h Urinary creatinine excretion will be measured via an AU408 Chemistry Analyzer
Timepoint [6] 415140 0
Pre- and post- each 21-day phase
Secondary outcome [7] 415141 0
Urinary nitrogen excretion will be adjusted for urinary creatinine excretion (to correct for completeness of 24-h urine collections) and dietary nitrogen intake on the days of urine collection.
Timepoint [7] 415141 0
Pre- and post- each 21-day phase

Eligibility
Key inclusion criteria
- Women aged between 65 and 90 y
- 24-h urine pH of less than or equal to 6.7 at screening
Minimum age
65 Years
Maximum age
90 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Self-reported history of conditions impacting acid-base balance (i.e. renal disease, addison’s disease, severe COPD with CO2 retention, kidney stones in last 2 years, liver cirrhosis), active hyperparathyroidism, untreated thyroid disease, significant immune disorders, unstable heart disease, primary aldosteronism, active malignancy, type 1 diabetes mellitus, active inflammatory bowel disease, neuromuscular disease (e.g. Myasthenia gravis, MS, muscular dystrophies, MND), Parkinson’s disease
• Medications that can impact acid-base balance, skeletal muscle / bone turnover (i.e. current use of diuretics, antacids containing aluminum hydroxide or magnesium hydroxide), HRT, insulin, drugs affecting bone turnover (bisphosphonates or denosumab in the last year, other osteoporosis medications [Tamoxifen/raloxifene, calcitonin, oestrogen] in the last 3 months, glucocorticoids for >10 days in the last 3 months), simvastatin / zocor, oestrogen suppressants , warfarin, anticoagulants other than aspirin (will be stopped 3 days prior to each biopsy)
• Glomerular filtration rate (GFR) <51 mL/min/1.73m2 and a serum potassium >5.3 mmol/L (assessed during participant screening)
• Regular resistance structured training (> 1 sessions of structured training / week)
• Participants taking nutritional supplements will be asked to cease taking these 2 weeks prior to, and for the duration of the study, including potassium-containing salt substitutes
• Total walking incapacity
• Women must be at least 1 year since last menses
• Smokers
• Bone mineral density (BMD) T-score below -2.5 at the lumbar spine or total hip
• Cachexia – defined as unintentional weight loss > 5% in last 6 months or, in persons with BMI < 20 kg/m2 weight loss > 2%, or low muscle mass (ASMI < 7 kg/m2 in men, < 5.5 kg/m2 in women) plus > 2% weight loss in individuals with an underlying condition associated with cachexia
• Current infectious disease or diagnosis of bloodborne disease
• Allergy to local anaesthesia
• Mini Mental State Examination (MMSE) score < 24
• If participant’s GP reports they have an excluded condition or are taking an excluded medication

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The allocation sequence will be uploaded to REDCap by an independent researcher who is not otherwise involved in the trial. Allocation will occur when participants are randomised via REDCap. Within REDCap, none of the investigators directly involved in the project will have access to the allocation sequence.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation, stratified by age, using a randomisation table generated using computer software.
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
Sample size was calculated based on the findings of Frassetto et al. (1) which reported a 5.7% decrease in urinary nitrogen excretion following 18-d of potassium bicarbonate supplementation in older women. Based on daily rates of MyoPS assessed in free-living older adults using the deuterated water method in our previous work (2), we calculated that a sample size of 16 would be sufficient to detect a difference in MyoPS between treatments of 0.09 %/d (equivalent to 5.7% increase in MyoPS) with a SD of 0.12 %/d, with an alpha of 0.05 and beta of 0.80 (G*Power v3.1). To protect study power and account for participant attrition, we will recruit a total of 20 participants.

Data will be analysed via repeated measures ANOVA.

1. Frassetto L, Morris RC, Jr., Sebastian A. Potassium bicarbonate reduces urinary nitrogen excretion in postmenopausal women. The Journal of clinical endocrinology and metabolism 1997;82(1):254-9. doi: 10.1210/jcem.82.1.3663.

2. Murphy CH, Flanagan EM, De Vito G, Susta D, Mitchelson KAJ, de Marco Castro E, Senden JMG, Goessens JPB, Miklosz A, Chabowski A, et al. Does supplementation with leucine-enriched protein alone and in combination with fish-oil-derived n-3 PUFA affect muscle mass, strength, physical performance, and muscle protein synthesis in well-nourished older adults? A randomized, double-blind, placebo-controlled trial. Am J Clin Nutr 2021. doi: 10.1093/ajcn/nqaa449.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
6/02/2023
Actual
16/03/2023
Date of last participant enrolment
Anticipated
5/06/2023
Actual
16/08/2023
Date of last data collection
Anticipated
14/08/2023
Actual
21/11/2023
Sample size
Target
20
Accrual to date
Final
20
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 38906 0
3000 - Melbourne

Funding & Sponsors
Funding source category [1] 312513 0
Government body
Name [1] 312513 0
Teagasc Agriculture and Food Development Authority
Country [1] 312513 0
Ireland
Funding source category [2] 312586 0
Other
Name [2] 312586 0
European Union (Horizon 2020 Marie Sklodowska-Curie Actions)
Country [2] 312586 0
Belgium
Primary sponsor type
Individual
Name
Dr Caoileann Murphy
Address
Exercise and Nutrition Research Program
Mary MacKillop Institute for Health Research
Australian Catholic University
Level 5, 215 Spring Street
Melbourne 3000 VIC
Country
Australia
Secondary sponsor category [1] 314196 0
Individual
Name [1] 314196 0
Prof John Hawley
Address [1] 314196 0
Exercise and Nutrition Research Program
Mary MacKillop Institute for Health Research
Australian Catholic University
Level 5, 215 Spring Street
Melbourne 3000 VIC
Country [1] 314196 0
Australia
Other collaborator category [1] 282473 0
Individual
Name [1] 282473 0
Prof Luc van Loon
Address [1] 282473 0
Department of Human Biology NUTRIM School of Nutrition and Translational Research in Metabolism,
Maastricht University Medical Centre,
P.O. Box 616, 6200 MD,
Maastricht
Country [1] 282473 0
Netherlands

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311848 0
Australian Catholic University Human Research Ethics Committee
Ethics committee address [1] 311848 0
Ethics committee country [1] 311848 0
Australia
Date submitted for ethics approval [1] 311848 0
04/08/2022
Approval date [1] 311848 0
24/10/2022
Ethics approval number [1] 311848 0
2022-2445HC

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

Contacts
Principal investigator
Name 122586 0
Dr Caoileann Murphy
Address 122586 0
Exercise and Nutrition Research Program,
Mary MacKillop Institute for Health Research,
Australian Catholic University,
Level 5, 215 Spring St,
Melbourne, VIC 3000
Country 122586 0
Australia
Phone 122586 0
+61 0468619003
Fax 122586 0
Email 122586 0
[email protected]
Contact person for public queries
Name 122587 0
Caoileann Murphy
Address 122587 0
Exercise and Nutrition Research Program,
Australian Catholic University,
Mary MacKillop Institute for Health Research,
Level 5, 215 Spring St,
Melbourne, VIC 3000
Country 122587 0
Australia
Phone 122587 0
+61 0468619003
Fax 122587 0
Email 122587 0
[email protected]
Contact person for scientific queries
Name 122588 0
Caoileann Murphy
Address 122588 0
Exercise and Nutrition Research Program,
Mary MacKillop Institute for Health Research,
Australian Catholic University,
Level 5, 215 Spring St,
Melbourne, VIC 3000
Country 122588 0
Australia
Phone 122588 0
+61 0468619003
Fax 122588 0
Email 122588 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
Potentially identifiable data


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.