ANZCTR - Registration

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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 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]

None

Universal Trial Number (UTN)

U1111-1194-0102

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

obesity

diabetes

cardiovascular disease

Condition category

Condition code

Diet and Nutrition

Obesity

Metabolic and Endocrine

Diabetes

Cardiovascular

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]

Prevention

Intervention code [2]

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]

Change in mood from baseline (POMS-SF)

Timepoint [1]

12 weeks

Primary outcome [2]

Change in carbohydrate withdrawal questionnaire (Symptoms-Q) from baseline

Timepoint [2]

12 weeks

Secondary outcome [1]

Change in triglyceride to HDL cholesterol ratio from serum assay

Timepoint [1]

Twelve weeks

Secondary outcome [2]

Change in HbA1c from serum assay

Timepoint [2]

Twelve weeks

Secondary outcome [3]

Change in total cholesterol to HDL ratio from serum assay,

Timepoint [3]

twelve weeks

Secondary outcome [4]

change in body fat percentage - measured by skinfold callipers at baseline and completion

Timepoint [4]

twelve weeks

Secondary outcome [5]

Change in waist to hip ratio as measured by tape measure at baseline and completion

Timepoint [5]

twelve weeks

Secondary outcome [6]

Change in serum urate (from serum assay)

Timepoint [6]

twelve weeks

Secondary outcome [7]

Change in c-reactive protein as measured y serum assay

Timepoint [7]

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

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Funding & Sponsors

Funding source category [1]

University

Name [1]

AUT University

Address [1]

17 Antares Place, Rosedale, Auckland 0632

Country [1]

New Zealand

Primary sponsor type

University

Name

AUT University

Address

17 Antares Place, Rosedale, Auckland 0632

Country

New Zealand

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Health and Disabilities Ethics Committees (HDEC)

Ethics committee address [1]

133 Molesworth Street, Thorndon, Wellington 6011

Ethics committee country [1]

New Zealand

Date submitted for ethics approval [1]

28/04/2017

Approval date [1]

16/06/2017

Ethics approval number [1]

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

Mr Cliff Harvey

Address

Holistic Performance Institute: 7 Ascension Place, Rosedale 0632, Auckland, New Zealand

Country

New Zealand

Phone

+64 9 478 3702

Fax

cliff@hpn.ac.nz

Contact person for public queries

Name

Cliff Harvey

Address

Holistic Performance Institute: 7 Ascension Place, Rosedale 0632, Auckland, New Zealand

Country

New Zealand

Phone

+64 9 478 3702

Fax

cliff@hpn.ac.nz

Contact person for scientific queries

Name

Cliff Harvey

Address

Holistic Performance Institute: 7 Ascension Place, Rosedale 0632, Auckland, New Zealand

Country

New Zealand

Phone

+64 9 478 3702

Fax

cliff@hpn.ac.nz

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

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Low-carbohydrate diets differing in carbohydrate restriction improve cardiometabolic and anthropometric markers in healthy adults: A randomised clinical trial.	2019	https://dx.doi.org/10.7717/peerj.6273

N.B. These documents automatically identified may not have been verified by the study sponsor.

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Documents added automatically