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. 2022 Aug 10;2022(8):CD015207. doi: 10.1002/14651858.CD015207

Gilleran 1996.

Study characteristics
Methods Study design: Randomised controlled trial
Study grouping: Parallel group
Country: United Kingdom
Setting: Intervention conducted in households in Birmingham; outcomes measured at a diabetic outpatient clinic
Aim of study: To assess the effect of dietary sodium reduction, and supplementation of potassium and magnesium, on blood pressure and metabolic parameters of hypertensive type 2 diabetics
Unit of allocation: adults (aged 18 years or older)
Start date: NR
End date: NR
Relevant study limitations as reported by study authors: Biochemical parameters, both in serum and urine, did not change to reflect changes in potassium and magnesium intake, and the authors ascribed this to the possibility that changes in dietary intake were not large enough to detect a difference. It was not possible to determine from this trial which of the three mineral interventions (sodium reduction, potassium increase, or magnesium increase) reduced blood pressure.
Sample size calculation: NR
Participants Baseline Characteristics
LSSS intervention

  • Age: in years, mean (SD): 62.5 (7.8)

  • Gender: Female, % (n/N): 40 (8/20)

  • Ethnicity/race: European

  • Smoking: NR

  • Body Mass Index (BMI): in kg/m2, mean (SD): 28.1 (4.6)

  • Blood pressure status: Hypertensive, % (n/N): 100 (20/20) participants with hypertension; duration of hypertension in years, mean (SD): 3.3 (4.6)

  • Antihypertensive medication used: On prior antihypertensive medication (stopped 1 month prior to randomisation), % (n/N): 45 (9/20)

  • Cardiovascular disease or stroke: NR

  • Diabetes mellitus: Type 2 diabetic, % (n/N): 100 (20/20); on hypoglycaemics, % (n/N): 50 (10/20); duration of DM in years, mean (SD): 3.9 (3.4)

  • Renal impairment: Hypertensive nephropathy (persistent proteinuria or raised serum creatinine > 130 µmol/L), % (n/N): 0 (0/20)

  • Dietary potassium intake: NR

  • Dietary sodium intake: NR

  • Urinary potassium excretion: mmol/24 h estimation, mean (SD): 58.8 (27)

  • Urinary sodium excretion: mmol/24 h estimation, mean (SD): 146.4 (73)


Control

  • Age: in years, mean (SD): 59.2 (10.8)

  • Gender: Female, % (n/N): 40 (8/20)

  • Ethnicity/race: European

  • Smoking: NR

  • Body Mass Index (BMI): in kg/m2, mean (SD): 28.6 (3.7)

  • Blood pressure status: Hypertensive, % (n/N): 100 (20/20) participants with hypertension; duration of hypertension in years, mean (SD): 2 (4.5)

  • Antihypertensive medication used: On prior antihypertensive medication (stopped 1 month prior to randomisation), % (n/N): 50 (10/20)

  • Cardiovascular disease or stroke: NR

  • Diabetes mellitus: Type 2 diabetic, % (n/N): 100 (20/20); on hypoglycaemics, % (n/N): 45 (9/20); duration of DM in years, mean (SD): 5.8 (5.8)

  • Renal impairment: Hypertensive nephropathy (persistent proteinuria or raised serum creatinine > 130 µmol/L), % (n/N): 0 (0/20)

  • Dietary potassium intake: NR

  • Dietary sodium intake: NR

  • Urinary potassium excretion: mmol/24 h estimation, mean (SD): 80.4 (32)

  • Urinary sodium excretion: mmol/24 h estimation, mean (SD): 168.9 (83)


Inclusion criteria: Established diabetic patients with hypertension, defined as three consecutive blood pressure readings of > 160 mmHg for systolic and > 95 mmHg for diastolic blood pressure. Participants who were on antihypertensives were included if they had ceased medication at least one month prior to the trial and met hypertensive criteria.
Exclusion criteria: Persons with poor or unstable diabetic control; on antihypertensive medication at the start of the study; who are treated with insulin; who had evidence of diabetic or hypertensive nephropathy, defined as persistent proteinuria on Albustix or elevated serum creatinine of 130 µmol/L; who have cardiac failure, are pregnant, or are already on a low‐sodium diet were excluded.
Pretreatment: None.
Method of recruitment of participants: Recruited from a diabetic clinic at a hospital in Birmingham
Informed consent obtained: Yes (written)
Clusters: n/a
Subgroups planned/measured: NR
Subgroups reported: NR
Participant flow
Assessed for eligibility: NR
Excluded (number with reasons): NR
Randomised: n = 40
Allocated to LSSS intervention(s): n = 20
Allocated to control: n = 20
Received allocated LSSS intervention(s): NR
Did not receive allocated LSSS intervention(s): NR
Lost to follow‐up (LSSS intervention group): n = 9 (n = 4 due to hypertensive criteria; n = 5 for other reasons)
Discontinued intervention (LSSS intervention group): n = 9 (n = 4 due to hypertensive criteria; n = 5 for other reasons)
Analysed (LSSS intervention group): n = 11
Excluded from analysis (LSSS intervention group): n = 0
Received allocated control: NR
Did not receive allocated control: NR
Lost to follow‐up (control group): n = 12 (n = 10 due to hypertensive criteria; n = 2 for other reasons)
Discontinued intervention (control group): n = 12 (n = 10 due to hypertensive criteria; n = 2 for other reasons)
Analysed (control group): n = 8
Excluded from analysis (control group): n = 0
Interventions Intervention Characteristics
LSSS intervention

  • Theoretical basis: Longer‐term dietary increases in potassium and magnesium combined with sodium reduction may have a therapeutic effect on the blood pressure and metabolic parameters of type 2 diabetics.

  • Description: Salt substitute (Seltin) (50% NaCl, 40% KCl, 10% MgSO4) used as added salt at the table by participants

  • LSSS category: ≥ 30% KCl

  • Contains fortificant: NR

  • Delivery: Discretionary use

  • Duration of run‐in period: 1 month

  • Duration of active intervention: 9 months

  • Duration of follow‐up (as reported): none

  • Total duration of study (as reported): 9 months

  • Timing: LSSS to be used throughout the study in cooking as well as for table salt.

  • Implementation: Unlabelled packs containing one container of LSSS (500 g) and two salt cellars (90 g) of LSSS were given monthly.

  • Providers: LSSS supplied by Cederoths (Sweden); unlabelled salt packs provided by investigators

  • Co‐interventions: NR

  • Resource requirements: NR

  • Integrity of delivery: Participants were asked about their salt use during dietary recall. Unlabelled packs and salt cellars were returned at each monthly visit and the amount returned was recorded, with good compliance defined as < 25% of the allotted LSSS. Good compliance was reported for 19/20 participants.


Control

  • Theoretical basis: To enable comparison of LSSS intervention with standard practice

  • Description: 'Ordinary' salt used as added salt at the table by participants

  • Contains fortificant: NR

  • Delivery: Discretionary use

  • Duration of run‐in period: 1 month

  • Duration of active intervention: 9 months

  • Duration of follow‐up (as reported): none

  • Total duration of study (as reported): 9 months

  • Timing: Ordinary salt to be used throughout the study in cooking as well as for table salt

  • Implementation: Unlabelled packs containing one container of ordinary salt (500 g) and two salt cellars (90 g) of ordinary salt were given monthly.

  • Providers: Ordinary salt supplied by Cederoths (Sweden); unlabelled salt packs provided by investigators. Ordinary salt supplied by Cederoths (Sweden); unlabelled salt packs provided by investigators

  • Co‐interventions: NR

  • Resource requirements: NR

  • Integrity of delivery: Participants were asked about their salt use during dietary recall. Unlabelled packs and salt cellars were returned at each monthly visit and the amount returned was recorded, with good compliance defined as < 25% of the allotted ordinary salt. Good compliance was reported for 19/20 participants.
Outcomes Primary outcomes: 

  • Diastolic Blood Pressure (DBP): Outcome measurement: Measurements with Hawksley random zero sphygmomanometer in supine (after 5‐min rest) and erect (after 2‐min rest) position by a blinded observer at follow‐up visits. Time points: 3, 6, 9 months

  • Systolic Blood Pressure (SBP): Outcome measurement: Measurements with Hawksley random zero sphygmomanometer in supine (after 5‐min rest) and erect (after 2‐min rest) position by a blinded observer at follow‐up visits. Time points: 3, 6, 9 months

  • Hypertension (as reported, or SBP > 140 mmHg or DBP > 85 mmHg): NR

  • Blood pressure control (achieving blood pressure threshold or 'control' as prespecified): NR

  • Cardiovascular events‐stroke: Outcome measurement: NR. Time points: 3 months

  • Cardiovascular events‐myocardial infarction: NR

  • Cardiovascular events‐other: NR

  • Cardiovascular mortality: NR

  • Blood potassium: NR

  • Hyperkalaemia: NR

  • Hypokalaemia: NR


Secondary outcomes: 

  • All‐cause mortality: NR

  • Adverse events: NR

  • Antihypertensive medication use: NR

  • Body Mass index (BMI): NR

  • Serum creatinine: NR

  • Albuminuria: NR

  • Urinary albumin‐to‐creatinine ratio (uACR): NR

  • Fasting blood glucose: NR

  • Blood triglycerides: Outcome measurement: Determined using specific enzymatic methods on Hitachi 737 and DAX 48 analysers. Time points: 3, 6, 9 months

  • Total blood cholesterol: Outcome measurement: Determined using specific enzymatic methods on Hitachi 737 and DAX 48 analysers. Time points: 3, 6, 9 months

  • 24‐h urinary sodium excretion: 24‐hour urine sample. Time points: 9 months

  • 24‐h urinary potassium excretion: 24‐hour urine sample. Time point: 9 months
Notes Funding source: NR
Authors name: P.M. Dodson
Institution: Department of Diabetes and Chemical Pathology, Birmingham Heartlands Hospital,
Email: paul.dodson@heartofengland.nhs.uk
Possible conflicts of interest (for study authors): NR
Sources used for data extraction: Journal article(s) with results of the trial
Trial registration details: NR
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk No information on how the randomisation sequence was generated
Allocation concealment (selection bias) Unclear risk Insufficient information on how the randomisation sequence was protected
Blinding of participants and personnel (performance bias)
All outcomes Low risk Participants were assigned to the intervention and control in a blinded manner. The intervention and control salts were provided in unlabelled packs, and participants found the LSSS and unlabelled salt to be palatable and indistinguishable from their salt intake prior to the intervention. Outcomes were unlikely to be affected by a lack of blinding.
Blinding of outcome assessment (detection bias)
All outcomes Low risk Blood pressure was measured by an observer blinded to treatment allocation using standard methods. It was not reported whether triglycerides and cholesterol were assessed blindly, but blood lipids are laboratory‐assessed outcomes unlikely to be influenced by a lack of blinding.
Incomplete outcome data (attrition bias)
All outcomes High risk Overall attrition was 5/20 (25%) in the intervention and 2/20 (10%) in the control group, all for 'other reasons'. These reasons were not explained in sufficient detail to determine whether withdrawal was differential by reason. An additional 4/20 (20%) in the intervention and 10/20 (50%) in the control group were withdrawn due to hypertensive criteria, and did not contribute further data to blood pressure and blood lipid outcomes.
Selective reporting (reporting bias) Unclear risk No study protocol or prospective trial registry entry available
Other bias Low risk None identified
Overall risk of bias High risk Unclear risk of bias for allocation concealment; high risk of bias for incomplete outcome data