Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000421336
Ethics application status
Approved
Date submitted
10/03/2017
Date registered
24/03/2017
Date last updated
4/06/2019
Date data sharing statement initially provided
20/03/2019
Date results information initially provided
20/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
How low do you need to go? Comparing symptoms of diet induction and mood with outcomes from diets containing differing levels of carbohydrate restriction.
Scientific title
Does a moderate carbohydrate restriction result in fewer symptoms of dietary induction and greater maintenance of mood, with comparable cardiometabolic results, when compared to more extreme carbohydrate restriction in healthy volunteers?
Secondary ID [1] 291400 0
None
Universal Trial Number (UTN)
U1111-1194-0102
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
obesity 302417 0
diabetes 302418 0
cardiovascular disease 302419 0
Condition category
Condition code
Diet and Nutrition 301986 301986 0 0
Obesity
Metabolic and Endocrine 302070 302070 0 0
Diabetes
Cardiovascular 302071 302071 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention is a dietary one. In a three-armed, controlled trial, participants will be provided a dietary plan to match their habitual calorie intake (as determined by a one-week lead in period), but modified to one of three reduced carbohydrate diets; 5% calories from carbohydrate, 15% calories from carbohydrate, and 25% calories from carbohydrate. Guidelines will be provided for protein intake which will be standardised to 1.4g of protein per kilogram of bodyweight for each participant, with fat making up the remainder of the calories allotted. The diet plan will be provided as a written plan, prepared by Cliff Harvey, a registered clinical nutritionist of 19 years experience and Caryn Zinn, a registered dietician of twenty years experience. The plan will include general nutritional guidelines for health, foods to be included and excluded in the diet and a menu plan tailored towards each participant and including three meals with portions determined by their calorie and macronutrient allotment. Two workshops will also be provided (by C.H) to provide additional information and support and to ensure participants understand the diet. These workshops will be provided in-person at AUT University for those able to attend and will also be broadcast live via webstream for those unable to attend in person. The workshops will be one hour in duration and will be conducted before the commencement of the trial. Throughout the intervention, participants will have access to the aforementioned practitioners to ask questions. The diet will be prescribed once for a 12-week trial. Information will be provided at AUT Millennium, 17 Antares Place, Rosedale, Auckland, 0632, New Zealand. As a free-living study, participants will be undertaking the diet in their own life environment. Throughout the study participants will have access to the practititioners (C.H and C.Z) via email, and telephone during business hours. Adherence will be monitored via online and app-based food diary (Fat Secret Pro).
Intervention code [1] 297437 0
Prevention
Intervention code [2] 297530 0
Lifestyle
Comparator / control treatment
The comparator group is one with a moderate carbohydrate restriction (to 25% calories)
Control group
Dose comparison

Outcomes
Primary outcome [1] 301408 0
Change in mood from baseline (POMS-SF)
Timepoint [1] 301408 0
12 weeks
Primary outcome [2] 301409 0
Change in carbohydrate withdrawal questionnaire (Symptoms-Q) from baseline
Timepoint [2] 301409 0
12 weeks
Secondary outcome [1] 332557 0
Change in triglyceride to HDL cholesterol ratio from serum assay
Timepoint [1] 332557 0
Twelve weeks
Secondary outcome [2] 332558 0
Change in HbA1c from serum assay
Timepoint [2] 332558 0
Twelve weeks
Secondary outcome [3] 332855 0
Change in total cholesterol to HDL ratio from serum assay,
Timepoint [3] 332855 0
twelve weeks
Secondary outcome [4] 332856 0
change in body fat percentage - measured by skinfold callipers at baseline and completion
Timepoint [4] 332856 0
twelve weeks
Secondary outcome [5] 332857 0
Change in waist to hip ratio as measured by tape measure at baseline and completion
Timepoint [5] 332857 0
twelve weeks
Secondary outcome [6] 332858 0
Change in serum urate (from serum assay)
Timepoint [6] 332858 0
twelve weeks
Secondary outcome [7] 332859 0
Change in c-reactive protein as measured y serum assay
Timepoint [7] 332859 0
twelve weeks

Eligibility
Key inclusion criteria
Non-obese, non-diabetic, between the ages of 25 and 49.
Minimum age
25 Years
Maximum age
49 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
BMI <19 or >30, diagnosed metabolic condition such as diabetes, or cardiovascular disease, chronic kidney or liver disease. Pregnancy or breastfeeding. Habitual intake of >40% calories from carbohydrate.

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)
Participants will be allocated into one of three groups and given a sealed envelope with their diet allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
By computer-generated, random number sequence
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
144 participants will be recruited. The calculation for participant numbers is based on the findings of the pilot study: The effect of medium chain triglycerides on time to nutritional ketosis and symptoms of keto-induction in healthy adults (manuscript submitted for publication). The primary outcome chosen for this power calculation is the change in POMS-TMDS from baseline. This measure was chosen as a validated questionnaire that is fit for our purpose of evaluating the effect of dietary induction on participants. In the pilot study, the mean POMS-TMDS was -11.4 in the control group (SD: 17.3) and -5.1 (SD: 7.2) in the experimental. We expect to see lowest mood disturbances in the non-ketogenic low carbohydrate diet (NKLCD) arm of the study compared to the very low carbohydrate ketogenic diet (VLCKD) arm. Assuming the ketogenic arm has a change from baseline of 11.4 (SD 17.4) and the minimum change in the NKLCD arm is +9.2 units higher with a restricted SD, as seen in the pilot (SD 7), then 36 participants per arm is required to detect this difference with a false positive (alpha) rate of 5% and false negative of (beta) 20%. We will allow for 48 per group to allow for dropouts based on the pilot.

Subjects will be compared with regard to baseline variables by treatment allocation arm to check for balance. Exploratory data analysis will consider the variation in different facets of the symptom scores with time from commencing the diet, by treatment arm, and by sociodemographic and clinical characteristics. Correlation between individual items in the score and baseline characteristics will be undertaken using principal components and biplots. Similar analyses will be carried out for associations between. Daily symptoms scores will be aggregated and summarised into mean changes from baseline. These changes will then be analysed by treatment group using ANOVA. These analyses will be compared with multiple linear regression, with baseline characteristics included in the regression model. Similarly, for secondary outcomes, changes in biomarker concentrations and anthropometry will be analysed using ANOVA and multiple linear regression. All tests will be two-tailed and the type-1 (false positive) error rate of 5% will be used to judge statistical significance.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
22/05/2017
Actual
7/08/2017
Date of last participant enrolment
Anticipated
23/06/2017
Actual
19/08/2017
Date of last data collection
Anticipated
Actual
10/12/2017
Sample size
Target
144
Accrual to date
Final
77
Recruitment outside Australia
Country [1] 8730 0
New Zealand
State/province [1] 8730 0

Funding & Sponsors
Funding source category [1] 295874 0
University
Name [1] 295874 0
AUT University
Country [1] 295874 0
New Zealand
Primary sponsor type
University
Name
AUT University
Address
17 Antares Place, Rosedale, Auckland 0632
Country
New Zealand
Secondary sponsor category [1] 294759 0
None
Name [1] 294759 0
Address [1] 294759 0
Country [1] 294759 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297153 0
Health and Disabilities Ethics Committees (HDEC)
Ethics committee address [1] 297153 0
133 Molesworth Street, Thorndon, Wellington 6011
Ethics committee country [1] 297153 0
New Zealand
Date submitted for ethics approval [1] 297153 0
28/04/2017
Approval date [1] 297153 0
16/06/2017
Ethics approval number [1] 297153 0
17/STH/60

Summary
Brief summary
Reduced carbohydrate diets offer benefits for the prevention and adjunct treatment of health conditions including; neurological disorders, cancer, obesity, diabetes and other conditions on the spectrum of metabolic syndrome. They are increasingly popular for mainstream and athletic use for weight-loss and maintenance and have been demonstrated to improve satiety and reduce hunger. But adaptation from a standard diet to one low in carbohydrates can cause various unpleasant symptoms, referred to in common parlance as ‘keto-flu’. These symptoms of carbohydrate restriction are assumed to provide a barrier to the use of, and compliance with low carbohydrate diets. However, these early-induction symptoms have not been well described in the scientific literature. So, at this time, it is not clear whether symptoms are related solely to keto-induction (i.e. in very low carbohydrate ketogenic diets) or are more generally, symptoms of carbohydrate withdrawal. Outcomes from ketogenic and non-ketogenic lower carbohydrate diets are likely to be similar and the degree to which people experience symptoms of carbohydrate withdrawal is also likely to influence compliance. For many, it may not be necessary to restrict carbohydrate to the degree necessary to achieve ketosis, especially if the symptoms resulting from extreme carbohydrate restriction are disproportionate to the beneficial outcomes from the diet. This has not been investigated and this study will seek to address this important clinical topic
Study Hypothesis:
A moderate restriction of carbohydrate results in fewer symptoms of dietary induction and greater tolerance and adherence to diet, with comparable results for cardiometabolic outcomes when compared to more extreme carbohydrate restriction.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 73154 0
Mr Cliff Harvey
Address 73154 0
Holistic Performance Institute: 7 Ascension Place, Rosedale 0632, Auckland, New Zealand
Country 73154 0
New Zealand
Phone 73154 0
+64 9 478 3702
Fax 73154 0
Email 73154 0
[email protected]
Contact person for public queries
Name 73155 0
Mr Cliff Harvey
Address 73155 0
Holistic Performance Institute: 7 Ascension Place, Rosedale 0632, Auckland, New Zealand
Country 73155 0
New Zealand
Phone 73155 0
+64 9 478 3702
Fax 73155 0
Email 73155 0
[email protected]
Contact person for scientific queries
Name 73156 0
Mr Cliff Harvey
Address 73156 0
Holistic Performance Institute: 7 Ascension Place, Rosedale 0632, Auckland, New Zealand
Country 73156 0
New Zealand
Phone 73156 0
+64 9 478 3702
Fax 73156 0
Email 73156 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Deidentified data-set including baseline and outcome measures blood and anthropometric measures, along with deidentified demographic data (age, and gender & ethnicity preference) will be available
When will data be available (start and end dates)?
From 1/2/2019 until 1/2/2022
Available to whom?
Researchers who request data
Available for what types of analyses?
Statistical analyses
How or where can data be obtained?
As a raw, deidentified R-file emailed to the researcher requesting data.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Harvey CJ, Schofield GM, Zinn C, Thornley SJ, Crof... [More Details]
Basic resultsNo 372524-(Uploaded-15-03-2019-14-09-45)-Basic results summary.docx
Plain language summaryNo Key findings: • Reduced carbohydrate diets have a... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseLow-carbohydrate diets differing in carbohydrate restriction improve cardiometabolic and anthropometric markers in healthy adults: A randomised clinical trial.2019https://dx.doi.org/10.7717/peerj.6273
N.B. These documents automatically identified may not have been verified by the study sponsor.