SalT Reduction InterVEntion: Examination of the Metabolic, Behavioral and Health Consequences of Reducing Salt Intake. A Randomized Controlled Trial in a Real Life Setting
Phase: NA
Conditions: Salt Intake
Sponsor: Bispebjerg Hospital

 
 
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Official title of the study: SalT Reduction InterVEntion: Examination of the 
metabolic, behavioral and health consequences of reducing salt intake. A 
randomized controlled trial in a real life setting. 
NCT number: Not yet assigned 
Date of the document: December 22, 2017 
 
 
English summary of the Danish Scientific Ethical Committee protocol 
 
 
 

 
 
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PROTOCOL SalT Reduction InterVEntion (STRIVE) 
 
Project Title  
English Title: SalT Reduction InterVEntion (STRIVE): Examination of the Metabolic, Behavioral and 
Health Consequences of Reducing Salt Intake. A Randomized Controlled Trial 
in a Real-Life Setting. 
 
Danish title: ”Brød og Sundhed: Undersøgelse af de stofskifte-, adfærds- og helbredsmæssige konsekvenser 
af at reducere saltindtaget? Et randomiseret kontrolleret forsøg ” 
 
Sponsor/ Collaborators 
Principal Investigator: Ulla Toft  
Official Title: Associate Professor, PhD, MSc, Head of Section of Health Promotion and Prevention; Center 
for Clinical Research and Prevention (CCRP) 
Affiliation: Bispebjerg Hospital 
 
Collaboration:  
The project is based on collaboration between several relevant partners: 
• Center for Clinical Research and Prevention (CCRP), Frederiksberg/Glostrup, Denmark (Ulla 
Toft, Kirsten Schroll Bjørnsbo and Allan Linneberg) 
• DTU Food; National Food Institute, Søborg, Denmark (Anne Dahl Lassen, Nanna Louise Riis and Ellen 
Trolle) 
• Danish Veterinary and Food Administration, Ministry of Environment and Food of Denmark 
(Hanne Høberg Hansen and Else Molander) 
• Clinical Physiology/Nuclear Medicine Section, Glostrup Hospital, Denmark (Niklas Rye Jørgensen) 
• Wolfson Institute of Preventive Medicine, London, UK (Graham MacGregor) 
• Lantmännen Cerealia A/S (Jan H. Poulsen). 
 
The project is funded by: The Danish Heart Foundation, The Capital Region of Denmarks’ Research 
Foundation, Axel Muusfeldt’s foundation, the Toyota Foundation, The Danish Technical University and 
Doctor Sofus Carl Emil Friis and wife Olga Doris’ grant 
 
Study aim 
This controlled randomized trial deals with 14+ weeks of intervention with a) bread with gradually reduced 
salt content, b) combination of salt-reduced bread and dietary counseling in comparison with a control 
group (bread with standard salt content). Participants will be recruited as families living in the local area of 
the production bakery in the southwestern part of the Capital Region of Denmark. The study aims to 
elucidate the metabolic, behavioral and health consequences of reducing salt intake and to explore the 
effect of different salt reduction strategies among families. 
 
Motivation for Salt intervention 
Excess dietary sodium has a major role in the pathogenesis of hypertension, a leading risk factor for 
premature death in the world [1,2]. The dietary salt intake in most countries worldwide, including 

 
 
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Denmark, is far beyond the recommended level (<5-6 gram/day) [3] and population-based salt reduction 
has been rated to be one of the most cost-effective strategies to prevent cardiovascular disease (CVD)[4,5]. 
A lower salt diet, if continued, may lessen the subsequent rise in blood pressure (BP) with age, which would 
have major public health implications in terms of preventing the development of hypertension and CVD 
later in life. In a report developed for the Danish Ministry of Food, Agriculture and Fisheries, we have 
estimated that a reduction in the mean salt intake of 3 gram/day in the Danish population would reduce 
fatal and non-fatal cases of CVD by 1,700-2,800 annually and reduce health care costs by up to two billion 
DKK per year [6].  Much less studies in this area are done among children. However, there is good evidence 
that salt intake plays an important role in regulating BP in children too [7]. Although the magnitude of the 
association between salt reduction and blood pressure in children is relatively modest, blood pressure 
follows a tracking pattern from childhood into adulthood; therefore, the public health benefits of shifting 
the distribution of population levels is important. Additional consequences of excess salt intake during early 
life include increased risk of obesity and the development of taste preferences for saltier foods [8]. 
 Several countries including Denmark have initiated national programs to decrease salt intake in the 
population [9,10]. However, some recent studies have shown a U-shaped association between sodium 
intake and cardiovascular disease and currently the effect of salt reduction on morbidity and mortality in 
the population is heavily discussed [9,11,12,13].  
In addition to a better understanding of the health effects of a reduced salt intake, there is a need for 
better evidence regarding effective strategies to reduce salt intake in Denmark and other similar countries. 
National programs to reduce salt intake on a population-based level relies mainly on food product 
reformulation as up to 80% of the salt intake in most countries comes from salt added to processed foods 
[14]. The biggest contributor of dietary sodium intake in Denmark is bread. Therefore, reducing the sodium 
content in bread could be a relevant part of an effective strategy to reduce the sodium intake of the Danish 
population. Because sudden large reduction of salt can make foods unacceptable to consumers [15], a 
gradual reduction of the salt content in small steps is generally recommended [3,16]. 
To meet the national goal of lowering salt intake by 3 g/d, reformulation of a single food cannot stand 
alone. Dietary counseling is another possible strategy to reduce salt intake.  
All in all, there is a need for high quality studies carried out in "real life settings" over a longer period. 
 
Objectives 
The overall aim of this study is to investigate the metabolic, behavioral and health consequences of 
reducing salt intake and to explore the effect of different salt reduction strategies among families. More 
specifically the objectives are: 
• to examine the effects of two different salt reduction interventions (A. gradually lowering salt 
content in bread; A+B. intervention combining salt reduced bread and dietary counseling) on the 
overall dietary intake (including salt), salt-taste sensitivity and preferences 
 
• to examine the (potential adverse) effects of different levels of salt reduction on selected 
cardiovascular risk factors (blood pressure, blood lipids, renin, aldosterone, noradrenaline, 
adrenaline, plasma glucose, Hb1AC, anthropometry) 
 
• to explore the mechanisms in the possible association between salt intake, sugar-sweetened soft 
drink consumption and obesity. 

 
 
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Methods 
The project will be carried out at the Center for Clinical Research and Prevention (CCRP), formerly known as 
Research Center for Prevention and Health (RCPH), 'The Population Surveys in Glostrup', which has more 
than 50 years of experience in conducting population surveys. Data collecton is scheduled to be completed 
during the period 1 January 2018 to August 2018 and it is expected that 450 children and adults divided 
into 120 families will participate. 
 
At baseline and endpoint participants will be examined about salt intake (24 hr urine collection, 7-day 
dietary record), salt preferences and salt sensitivity, blood pressure, anthropometry, blood lipids, sugar 
metabolism and hormones. The intervention will last 14+ weeks.  
 
Study Design 
STRIVE (SalT Reduction InterVEntion) is a single blinded, cluster randomized controlled trial, with children 
and adults recruited as families and randomly assigned to three parallel intervention arms (A: salt reduced 
bread; A+B: Salt reduced bread and dietary counseling; C: Bread with standard salt content).  
Children and parents are targeted as families, to reflect the real life setting that salt is consumed in and 
because interventions that target the whole family, rather than single participants, are more effective for 
achieving dietary goals. 
For a period of 14+ weeks, bread (rye bread, wheat bread and buns) will be delivered twice a week to the 
families, either as bread with gradually reduced salt or with a standard salt content.  
All families start with a run-in period of bread with standard salt content, which is gradually lowered in 
intervention group A and A+B during the first month. The bread intervention begins after the baseline 
health examination (including urine collection and dietary record) has been completed and runs until data 
from the endpoint study has been collected.  
Questionnaire 
Information on socio-economic background, general health, smoking habits, physical activity, salt intake 
and knowledge on diet will be obtained through a short questionnaire. Questions are developed, tested 
and applied for use in Danish National Surveys 
 
Health examination 
Families are invited to attend a health examination at the research center at baseline and at endpoint. At 
both visits all participants will have a general health examination including measurement of blood pressure, 
weight, height, and waist circumference as well as semi-fasting blood samples. (No children < 10 years, but 
children 10 – 17 can volunteer for a blood sample, blood test is compulsory in adults). 
Each donor delivers a maximum of 50 milliliters of blood, which corresponds to 1/10 of a normal blood 
donor loss. 
For the testing of microalbuminuria all participant will make a spot urine sample during the health 
examination day. 
Participants (> 10 years) will participate in a salt preference and sensitivity test. Participants are asked to 
order bread of varying salt content according to their preference. They will also indicate in a line of 
different salt solutions when they can taste, that the solution is different from water. 

 
 
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Furthermore, participants will collect 24-hour urine 3 days (children only one day) and register their dietary 
intake during the following 7 days (web-based, estimated portion sizes dietary record) within the week 
after the health examination both at baseline and at endpoint.  
Repeated 24-hour urine collections and 7 days dietary records are chosen, because these methods are the 
most valid methods to estimate salt intake and the overall dietary intake on an individual level. To verify 
the completeness of the 24-hour urine collections the PABA (Para-aminobenzoic acid) method is applied in 
adults.  
 
Urine Collection 
Participants will receive materials for three 24hr urine collection; a brown bottle (3 L), a smaller ‘visiting 
bottle’ (0.5L), a safety pin for attachment to a suitable place as a reminder. Each family will receive a large 
backup bottle (5L) as a backup, a funnel and a urinary hat for the toilet, to aid urine collection. Adults are 
given three urine monovettes per day and children two for collection of urine aliquots after the completion 
of each 24 hr collection period. A pen to mark containers and monovettes with name, day and volume. 
For validation adults are given 3*3 80mg PABA tablets (Glostrup Hospital Pharmacy). 
Participants will also receive a form to register beginning and ending of the collection periods, PABA 
administration and exceptions to the protocol (ie estimation of urine loss, medicine).  
Adults will be instructed to collect 24 h urine for three consecutive days (1 weekend day, 2 working days) 
and children for 1 day (weekend day).  
Seven-day web-based dietary record  
All participants must record their dietary intake for seven days at baseline and at endpoint using a web-
based dietary record system. Each of the seven days participants will be guided through the meals of the 
days and asked to indicate the food consumed as well as the portion size based on images. Participants will 
receive verbal and written instructions in the use of the web-based system as well as a link to a video 
instruction. Parents will assist the registration of their children. Reminders will be send, if the record hasn’t 
been completed the day before. 
 
Biochemical analyses 
In the blood samples, biomarkers are determined for fat metabolism (total cholesterol, HDL, LDL, 
triglycerides), sugar metabolism (plasma glucose, and HbA1C), hormones (aldosterone, renin, adrenaline 
and noradrenaline).  
Urine samples will be analyzed for creatinine, sodium, potassium and in spot urine albumin will also be 
determined. These biomarkers are continuously analyzed at the Clinical Biochemistry Department at 
Rigshospitalet, Glostrup.  
In addition to the above, biological material (urine, serum / plasma and whole blood) is stored for later 
research. The biological material is stored for up to 50 years (31 December 2068) after which the material is 
destroyed.  
The purpose of the research biobank is to secure biological material for future research. The material will 
be unique as it represents representative samples of the population. This ensures a preparedness for public 
health research in the future. Participants provide informed written consent for the storage of biological 
material in research biobank. When a future research project wishes to use the biobank for purposes not 
covered by this protocol, the investigators shall ensure the retrieval of informed consent or seek exemption 
from this requirement by the Scientific Ethics Committee. 
 

 
 
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Dietary counselling  
Participants in intervention group B will receive dietary counselling on top of salt reduced bread, to further 
reduce dietary salt and increase potassium. The group-based tuition will include official guidelines on salt 
and healthy diet (especially fruit and vegetables rich in potassium). Hereafter families will be invited to an 
individual meeting setting goals for reducing sodium and increasing potassium. To reinforce compliance 
families will receive weekly newsletters and two telephone calls. 
 
Participants and Recruitment procedures 
In January – February 2018 families will be recruited through digital and paper advertisements posted in 
social media, schools, kindergartens and companies sited in five municipalities (Albertslund, Ballerup, 
Egedal, Glostrup and Rødovre) in the southwestern part of the Capital Region of Denmark. The area is 
selected to be close to either Smørum Konditori, the baker that produces the intervention bread, or the 
research center (Center for Clinical Research and Prevention, Glostrup Hospital), where the health 
examinations will take place.  
Families are defined as minimum one child and one parent living together. Children, who lives fifty percent 
of their time with each of their divorced parents, will be able to participate if both parents join the study.  
Participants will be screened to identify participants living with children between 3 and 17 years and with a 
daily intake of both white and/ or brown bread (> 175 gram of bread/day. Exclusion criteria are: 
antihypertensive and lipid-lowering treatment, pregnancy, diabetes, coronary heart disease, urine albumin 
greater than 300 mg/day. 
At the end of the baseline health examination families will be systematically randomized by a computer 
into one of the three groups. In divorced families, both parents (and their families) will follow the 
randomization of the parent first examined.  
 
Publication of experimental results 
Both "negative" and "positive" as well as inconclusive results will be published in scientific journals under 
the Vancouver rules. 
 
 
References 
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intake. Nutr Metab Cardiovasc Dis 2011; 21(9):617-619.  
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health: systematic review and meta-analyses. BMJ 2013; 346, 1-20  
3. World Health Organization. Report of the Formal Meeting of Member States to conclude the work on the 
comprehensive global monitoring framework, including indicators, and a set of voluntary global targets for 
the prevention and control of noncommunicable diseases. Report, 1-6, Geneva, Switzerland: WHO Press, 
Worlds Health Organization; 2012.  
4. Scientific Report of the 2015 Dietary Guidelines Advisory Committee. Advisory Report to the Secretary of 
Health and Human Services and Secretary of Agriculture. Feb. 2015.  
5. Cobiac L, Vos T, Veerman J. Cost-effectiveness of interventions to reduce dietary salt intake. Heart 2010; 
96(23):1920-192.  

 
 
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Fødevarestyrelsen, februar 2012.  
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