Application of n-of-1 Clinical Trials in Personalized Nutrition Research: A Trial Protocol for Westlake N-of-1 Trials for Macronutrient Intake (WE-MACNUTR)

Abstract

Personalized dietary recommendations can help with more effective disease prevention. This study aims to investigate the individual postprandial glucose response to diets with diverse macronutrient proportions at both the individual level and population level, and explore the potential of the novel single-patient (n-of-1) trial for personalization of diet. Secondary outcomes include individual phenotypic responses and the effects of dietary ingredients on the composition of gut microbiota. Westlake N-of-1 Trials for Macronutrient Intake is a multiple crossover feeding trial consisting of 3 successive 12-d dietary intervention pairs including a 6-d washout period before each 6-d isocaloric dietary intervention: a 6-d high-fat, low-carbohydrate diet, and a 6-d low-fat, high-carbohydrate diet. The results will help provide personalized dietary recommendations for macronutrients in terms of postprandial blood glucose responses. The proposed n-of-1 trial methods could help in optimizing individual health and advancing health care. This trial was registered with clinicaltrials.gov (NCT04125602).

Keywords: dietary intervention; gut microbiome; high-fat diet; low-carbohydrate diet; n-of-1; personalized nutrition; postprandial blood glucose; single patient trial.

© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society for Nutrition.

Figures

FIGURE 1

The development of personalized nutrition. Personalized nutrition was born in the context that a conventional “one-size-fits-all” approach usually fails to meet an individual's nutritional requirements. An “n-of-1” clinical trial is a novel study design for the investigation of personalized nutrition, contrasting with traditional designs such as the observational study or randomized controlled trial. Integration of multiomics data, including nutrigenomics, proteomics, metabolomics, microbiome, and other phenotypes, is key for the development of personalized nutrition.

FIGURE 2

Flow diagram of the Westlake N-of-1 Trials for Macronutrient Intake (WE-MACNUTR) trial. The flowchart summarizes the preparation phase and Set 1 of the trial. Sets 2 and 3 share the same trial design as Set 1 except for no blood sample collection for washout or intervention period. The sequence of 2 types of 6-d dietary interventions in each set is randomized using a block randomization as LF-HC and HF-LC diets in Set 1; HF-LC and LF-HC diets in Set 2; and HF-LC and LF-HC diets in Set 3. CGM, continuous glucose monitoring; GI, gastrointestinal; HF-LC, high-fat, low-carbohydrate; LF-HC, low-fat, high-carbohydrate.

FIGURE 3

The timeline of the Westlake N-of-1 Trials for Macronutrient Intake (WE-MACNUTR) trial. The timeline illustrates a preparation period for participant recruitment, a baseline data collection period, and 3 feeding trial periods. The first set of the trial consists of 2 washout periods (highlighted in gray) and 2 randomized dietary intervention periods (highlighted in green). In all 3 sets of the trial, both washout and intervention periods last for 6 d.

FIGURE 4

Representation of the hierarchical Bayesian estimation for the primary outcomes at both individual and population level (a combination of single-patient studies). The observed repeated measurements of the peak postprandial glucose concentrations for a given patient are combined into a sample mean and a sample variance. The model assumes that the patient's measurements follow a normal distribution centered about that patient's true mean effect (μi) with variance σ12. At the population level, the various patients’ true means (μi) are assumed to follow a normal distribution centered about an overall population mean (μ0) with between-patient variance τ2. For the Bayesian specification, prior distributions are assigned for β, μ0, σ12, and τ2. In the present study, these prior distributions are standard noninformative prior distributions. X represents the independent variable: dietary patterns (high-fat and low-carbohydrate compared with low-fat and high-carbohydrate). Secondary and exploratory outcomes will be analyzed similarly. PMG, postprandial maximum glucose.