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Trial registered on ANZCTR


Registration number
ACTRN12620001278921p
Ethics application status
Submitted, not yet approved
Date submitted
23/10/2020
Date registered
26/11/2020
Date last updated
26/11/2020
Date data sharing statement initially provided
26/11/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of a low carbohydrate diet on heart failure symptoms and quality of life in patients with diabetic cardiomyopathy.
Scientific title
Effects of a low carbohydrate diet on heart failure symptoms and quality of life in patients with diabetic cardiomyopathy.
Secondary ID [1] 302617 0
Nil Known
Universal Trial Number (UTN)
U1111-1260-0996
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetic cardiomyopathy 319509 0
Heart failure 319510 0
Type 2 Diabetes Mellitus 319511 0
Condition category
Condition code
Cardiovascular 317466 317466 0 0
Other cardiovascular diseases
Metabolic and Endocrine 317467 317467 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention group (low carbohydrate diet):
For the purpose of this study, participants will be coached by the student researcher who will be guided by a qualified dietitian, to follow a LC diet as defined by an intake of less than 130g of carbohydrate per day (Hite et al., 2019). To achieve a CHO ingestion of less than 130g per day, the participants will be instructed to enjoy a variety of above ground and green, leafy vegetables. Small amounts of fruit, starchy vegetables such as potatoes, sweet potatoes, parsnip, peas and corn, nuts/seeds and legumes are permitted. Participants are encouraged to eat freely from animal and plant proteins such as chicken, fish, unsweetened dairy products and tofu. Participants will be coached to avoid high CHO foods such as bread, rice, pasta, sweetened beverages and alcohol. Food lists using a “traffic light system” will be provided to the participants as a reference and to enhance compliance with the diet. These lists categorise foods and drinks into: Always/every day (green list), sometimes (orange list) and avoid (red list).

Minimum Dietary protein intake level will be set to 1.2 – 1.7 g/kg of ideal body weight, in keeping with both the Clinical Guidelines for Therapeutic Carbohydrate Restriction (Hite et al., 2019) and the Australian Dietary Guidelines (National Health and Medical Research Council, 2013). Dietary fat intake will not be restricted. Dietary sodium intake will be limited to <2g/day in accordance with The National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand guidelines for the prevention, detection, and management of HF in Australia (Atherton et al., 2018).

A 16-week time frame for the intervention has been proposed. In the first month the participants will be introduced to the low carbohydrate diet. Participants will be invited to attend a 60-minute group counselling session, once per week in the first 4 weeks and fortnightly individual 60-minute sessions for the following 12 weeks. Sessions will be held face to face, via phone call or via video conferencing if the participants prefer. Participants will be requested to change their diet gradually over the initial four weeks and should ideally have adjusted all their meals to the low carbohydrate recommendations when attending the fourth session at the end of the first month. The counselling sessions will focus on discussion of the underlying mechanisms that drive type 2 diabetes and heart failure, instructions on dietary carbohydrate restriction, food selection and meal preparation, interpretation of food labels, recognition of potential side effects, establishing mindful eating techniques, difficulties in adhering to the diet and support for health behaviour change. Dietary counselling will be adapted to the personal, as well as the religious and cultural food preferences of the participants. All study participants will be offered the opportunity to invite a member of their family/household to attend the education sessions if they chose.

Participants will be asked to complete three 24-hour dietary recalls using the validated INTAKE-24 AUS computerised dietary recall system (Simpson et al., 2017). The recall diary will specifically monitor the food intake of two weekdays and one weekend day at baseline, week six and at the end of the intervention (week 16). This way, the extent of the patient’s dietary changes will become apparent.

INTAKE-24 AUS is based on the original web-based system INTAKE-24 UK, developed by researchers at the Human Nutrition Research Centre at Newcastle University (Simpson et al., 2017). INTAKE-24 AUS provides a reliable, affordable and user friendly 24-hour dietary recall system (Simpson et al., 2017). Based on the multiple-pass 24-hour recall (Raper et al., 2004), INTAKE-24 AUS includes an extensive variety of foods commonly eaten in Australia, linked to nutrient composition codes (Foster et al., 2019). As the user is prompted through the recall process, the inclusion of food images enables easy portion size estimation by participants without the need for weighing of food (Simpson et al., 2017). The advantage of this web-based recall system compared to other methods is that it enables the participant to complete the recall where and when it is convenient for them. In addition to this, participants will be invited to complete a mini food frequency questionnaire (FFQ). The food questionnaire is a self-administered assessment tool to estimate food frequency intake over a specific period of time.

Dietary counselling will be adapted to the personal, as well as the religious and cultural food preferences of the participants.



Intervention code [1] 318902 0
Lifestyle
Intervention code [2] 318903 0
Treatment: Other
Comparator / control treatment
The control group (CG):
Participants randomised to the control group will be supplied with the “Living Well with Heart Failure” resource (The National Heart Foundation of Australia, 2018). Additionally, participants in the CG group will be counselled to adopt a heart-healthy diet as defined by The National Heart Foundation of Australia (2019). https://www.heartfoundation.org.au/heart-health-education/healthy-eating

Specifically, participants will be asked to:
• Eat a variety of fruit and vegetables
• Consume wholegrains such as whole meal pasta, rice and bread
• Include protein-rich foods such as legumes, fish and poultry
• Choose unflavoured dairy products and cheese
• Include foods containing heart-healthy fats such as nuts, olives and avocados
• Avoid processed and baked goods, sugar sweetened beverages and fast foods
• Limit dietary sodium intake to <2g/day (Atherton et al., 2018)

Participants will also be invited to maintain three 24-hour food recalls in line with the low carbohydrate intervention group.

To ensure similar intensity of intervention and to avoid bias, the control group will be coached by a research assistant who is trained to educate the participants to follow a heart-healthy diet as defined by The National Heart Foundation of Australia (2019). Participants will be invited to attend a 60- minute group counselling session at the beginning of the study (week 1). Additionally, Participants will receive a follow-up phone call by the research assistant (week 6), to assess diet adherence and answer any questions participants may have.
Control group
Active

Outcomes
Primary outcome [1] 325500 0
NYHA class, thirst and QoL are closely linked in heart failure patients. Changes to these parameters significantly change disease outcomes. A composite endpoint was chosen as dietary changes may impact on one or more of these parameters. The composite endpoint of this study is based on a study by Philipson et al., (2013) who assessed the effects of salt and fluid restriction on chronic heart failure patients.

Outcome of the primary composite endpoint after four months is defined as below.

Deterioration:
Participants will be classified as having deteriorated if any of the following criteria are present: Decline in NYHA by at least one class from baseline assessed by a heart failure clinician.

Increased frequency of lower limb swelling (greater than or equal to 1 rating assessed using a five-point Likert scale part of the KCCQ).
Increased thirst (greater than or equal to two points assessed using the Thirst Distress Scale)
Reduction in QoL (greater than or equal to four points determined using the KCCQ)

Improvement:
Participants will be considered as improved if none of the above criteria are met and they demonstrate at least one of the following:
Improvement in NYHA by one class from baseline
Decreased frequency of lower limb swelling (greater than or equal to 1 rating on a five-point Likert scale part of the KCCQ)
Decreased thirst (greater than or equal to two points on the Thirst Distress Scale)
Improved QoL (greater than or equal to four points on the KCCQ)
Weight reduction greater than two kg

Unchanged:
Participants who do not meet any of the above criteria will be classified as unchanged.
Timepoint [1] 325500 0
Timepoints for each element of the composite outcome will be as follows:

NYHA class will be measured at baseline and at four months post-commencement of diet.
Thirst will be measured at baseline and at four month post-commencement of diet.
QoL will be assessed at baseline and at four months post commencement of diet.
Lower limb swelling will be assessed at baseline and at four months post commencement of diet.
Secondary outcome [1] 388180 0
Changes in HbA1C by at least 2% in either (intervention or control) study group (McKenzie et al., 2017).
HbA1C levels will be assessed via routine blood test (5ml blood in lithium heparin tube) and immunoassay.
Timepoint [1] 388180 0
HbA1C will be measured at baseline and at four months post-commencement of diet.
Secondary outcome [2] 389155 0
Any hospitalisations for exacerbation of heart failure will be identified via review of the participant's medical record.
Timepoint [2] 389155 0
Hospitalisations will be assessed at four months post commencement of diet.
Secondary outcome [3] 389156 0
Mortality will be identified via review of the participant's medical records.
Timepoint [3] 389156 0
Mortality will be evaluated at four months post commencement of diet.
Secondary outcome [4] 389157 0
Change in weight of more than two kilograms assessed using a standard hospital scale.
Timepoint [4] 389157 0
Weight will be assessed at baseline and at four months post commencement of diet.

Eligibility
Key inclusion criteria
• Patients over the age of 18
• Diagnosis of HF based on echocardiography and/or Boston criteria
• Patients diagnosed with T2DM (HbA1C greater than or equal to 6.5)
• Patients not diagnosed with T2DM but diagnosed with IR as defined by a triglyceride and glucose index (TyG)* value of >4.49
• Patients who speak and understand sufficient English to consent.
• Access to an electronic device with internet connection

*Participants who are not diagnosed with T2DM but would like to enter the study may undergo screening for IR. The TyG is a simple, cost effective and reliable tool to identify IR in an individual. It is established through the equation:

TyG = Ln [fasting triglyceride (mg/dl) x fasting glucose (mg/dl)] / 2

The cut off for IR is placed at the TyG index of 4.49 with a sensitivity of 82.6% and specificity of 82,1% (AUC = 0.889, 95% CI: 0.854-0.924). The serum triglyceride levels, and glucose levels needed to establish IR will be ordered as part of the usual care for patients in the HF clinic.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

• Patients with T1DM may not be appropriate for the LC diet intervention due to their strict insulin requirements
• Patients with T2DM who require insulin
• Patients taking SGLT-2 inhibitors. There is a small risk of euglycaemic ketoacidosis in patients who take SGLT-2 inhibitors and simultaneously follow a low carbohydrate diet.
• Patients who are unable to give informed consent
• Patients suffering from cardiac cachexia as defined by an unintentional non-oedematous weight loss of >5% over at least six months. Cardiac cachexia is a sign of advanced heart failure. It is defined by muscle wasting and systemic inflammation. Patients with cardiac cachexia have strict energy and nutritional requirements and are therefore not suitable for this study.

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)
allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be undertaken using a random allocation software, https://www.randomizer.org.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Descriptive statistics for continuous variables will be used to describe the mean (standard deviation) or median (25th and 75th percentiles; interquartile range (IQR)). Frequencies and Chi-square will be used to describe categorical variables. Data will be analysed on an intention-to-treat basis. Any missing data will be followed up with the patient after each visit. Missing data will not be included in the analysis. For categorical variables, Independent T-test statistics will be used to compare independent samples. Comparisons of intervention and control group participants will use logistic regression models (with odds ratio (OR) and 95% confidence intervals for binary variables), logistic regression for categorical variables and linear regression for approximately normally distributed continuous variables. Statistical significance was defined as a p-value less than 0.05 (2-sided). All analyses will use SPSS version 26 (SPSS Inc., Chicago, Illinois).

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
11/01/2021
Actual
Date of last participant enrolment
Anticipated
1/04/2021
Actual
Date of last data collection
Anticipated
2/08/2021
Actual
Sample size
Target
80
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 17895 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 17896 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment postcode(s) [1] 31752 0
3084 - Heidelberg
Recruitment postcode(s) [2] 31753 0
3220 - Geelong

Funding & Sponsors
Funding source category [1] 307049 0
University
Name [1] 307049 0
Deakin University
Country [1] 307049 0
Australia
Primary sponsor type
Individual
Name
Professor Andrea Driscoll
Address
145 Studley Road PO Box 5555, Heidelberg, VIC 3084
Country
Australia
Secondary sponsor category [1] 307614 0
None
Name [1] 307614 0
N/A
Address [1] 307614 0
N/A
Country [1] 307614 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 307173 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 307173 0
Ethics committee country [1] 307173 0
Australia
Date submitted for ethics approval [1] 307173 0
28/10/2020
Approval date [1] 307173 0
Ethics approval number [1] 307173 0

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

Contacts
Principal investigator
Name 106290 0
Prof Andrea Driscoll
Address 106290 0
Austin Health, 145 Studly Road, PO Box 5555, Heidelberg, Vic 3084
Country 106290 0
Australia
Phone 106290 0
+61 03 94964626
Fax 106290 0
Email 106290 0
andrea.driscoll@austin.org.au
Contact person for public queries
Name 106291 0
Sabine Kleissl-Muir
Address 106291 0
Deakin University, Waterfront Campus 1, Gheringhap Street, Geelong VIC 3220
Country 106291 0
Australia
Phone 106291 0
+61 0492 972 887
Fax 106291 0
Email 106291 0
skleisslmuir@deakin.edu.au
Contact person for scientific queries
Name 106292 0
Andrea Driscoll
Address 106292 0
Austin Health, 145 Studly Road, PO Box 5555, Heidelberg, Vic 3084
Country 106292 0
Australia
Phone 106292 0
+61 03 94964626
Fax 106292 0
Email 106292 0
andrea.driscoll@austin.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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
EmbaseEffects of a low carbohydrate diet on heart failure symptoms and quality of life in patients with diabetic cardiomyopathy: A randomised controlled trial pilot study.2023https://dx.doi.org/10.1016/j.numecd.2023.08.015
N.B. These documents automatically identified may not have been verified by the study sponsor.