Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT04631913 |
| Other study ID # |
QUAKER - Oats & glycemia |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
August 14, 2020 |
| Est. completion date |
November 30, 2021 |
Study information
| Verified date |
November 2020 |
| Source |
University of Toronto |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Oats are a commonly consumed source of viscous soluble fibre, which has an established role
in cardiovascular disease risk management including in cholesterol and glycemic control. Oat
beta-glucan is recognized for its cholesterol-lowering effects with approved health claims in
Canada, US and Europe. However, the efficacy of oat beta-glucan on glycemic control is not
clear. We propose to conduct a systematic review and meta-analysis to explore the efficacy of
whole grain oats and oat beta-glucan on markers of glycemic control in people with, without
or at risk for diabetes.
Description:
RATIONALE Although oat beta-glucan has approved health claims in Canada, US, and Europe [1-3]
and is recognized by major cardiovascular guidelines [4,5] for its cholesterol-lowering,
there are no approved health claims for the maintenance or achievement of normal blood
glucose [6] and its role in the prevention and management of diabetes are less clear. We are
not aware of any systematic reviews and meta-analyses of prospective cohort studies of the
relation of the intake of whole oats, oat products, or oat beta-glucan with diabetes risk.
Although there are several systematic reviews and meta-analyses of randomized trials showing
that oats and oat beta-glucan improve markers of glycemic control and insulin resistance
[7-9], the census for theses analyses do not include new RCTs [10]. Similar to an evidence
synthesis that we conducted for all viscous fibers (inclusive of oat beta-glucan) [11], we
propose to conduct the "gold-standard: in evidence synthesis (a systematic review and
meta-analysis of randomized trials using Grading of Recommendations Assessment Development
and Evaluation [GRADE] system) to quantify and assess the certainty of the evidence for the
effect of oats and oat beta-glucan on established targets for glycemic control including
HbA1c, fasting glucose, fasting insulin, and measures of insulin sensitivity in participants
stratified by their risk of diabetes.
OBJECTIVES To quantify and assess the certainty of the evidence for the effect of oats and
oat beta-glucan on established targets for glycemic control including HbA1c, fasting plasma
glucose (FPG), 2h-plasma glucose (2h-PG), fasting plasma insulin, and measures of insulin
sensitivity and beta-cell function in participants who have diabetes, are at risk of diabetes
(prediabetes, metabolic syndrome, or overweight/obese), or are otherwise healthy.
DESIGN We will follow the Cochrane Handbook for Systematic Reviews of Interventions [12] and
report according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
(PRISMA) [13]. The protocol will be registered at www.clinicaltrials.gov.
DATA SOURCES MEDLINE, EMBASE, and The Cochrane Central Register of Controlled Trials will be
searched for eligible trials. We will also supplement our search with manual searches.
STUDY SELECTION We will include randomized controlled trials of ≥2-weeks assessing the effect
of whole grain oats or oat beta-glucan compared with a suitable non-oat control on
established targets for glycemic control including HbA1c, fasting plasma glucose, 2h-plasma
glucose (2h-PG), fasting plasma insulin, and measures of insulin resistance in participants
with or without diabetes.
DATA EXTRACTION Two or more investigators will independently extract relevant data. Authors
will be contacted for additional information and any missing data will be computed/imputed
using standard formulae [12].
RISK OF BIAS Two or more investigators will independently assess risk of bias using the
Cochrane Risk of Bias 2.0 Tool.
OUTCOMES The outcomes will include established targets for glycemic control including HbA1c,
fasting plasma glucose (FPG), 2h-plasma glucose (2h-PG), fasting plasma insulin, and measures
of hepatic insulin sensitivity (HOMA-IR, hyperinsulinemic euglycemic clamp) whole body
insulin sensitivity (Matsuda OGTT-ISI, frequently sampled intravenous glucose tolerance test
[FSIGTT], hyperinsulinemic-euglycemic clamp) and beta-cell function (insulin secretion index,
ISSI-2).
DATA SYNTHESIS Data will be pooled using the Generic Inverse Variance method stratified by
risk of diabetes. Random effects models will be used with paired analyses applied to
crossover designs [14]. Heterogeneity will be assessed (Cochran Q statistic) and quantified
(I2 statistic). Sources of heterogeneity will be explored by sensitivity analyses. If ≥10
trial comparisons are available, a priori subgroup analyses will also be conducted to explore
sources of heterogeneity (dose, comparator, intervention form (whole grain oat or oat
beta-glucan) follow-up, baseline levels, design, body weight change, saturated fat intake,
carbohydrate intake, protein intake, intervention food matrix, oat beta-glucan molecular
weight and risk of bias). Meta-regression will assess the significance of subgroup analyses.
Linear and nonlinear dose-response analyses will be assessed by generalized least squares
trend (GLST) estimation models and spline curve modelling (MKSPLINE procedure), respectively.
When ≥10 trial comparisons are available, publication bias will be assessed by inspection of
funnel plots and the Egger and Begg tests. Adjustment for evidence of funnel plot asymmetry
or small study effects will be conducted by the Duval and Tweedie trim-and-fill method.
GRADE ASSESSMENT To assess the certainty of the evidence, we will use the GRADE system, an
evidence-based grading system adopted by >100 organizations
(http://www.gradeworkinggroup.org/). It grades the evidence as high, moderate, low or very
low quality based on the study design and a series of downgrades (risk of bias, imprecision,
inconsistency, indirectness, publication bias) and upgrades (large magnitude of the effect,
dose-response gradient, and attenuation by confounding). We will follow the GRADE handbook
(https://gdt.gradepro.org/app/handbook/handbook.html) and use the GRADEpro (GRADEprofiler)
software Version 3.2.
KNOWLEDGE TRANSLATION PLAN FOR IMPACT We will follow the Ottawa model of Research for
knowledge translation [15]. The results will be disseminated through interactive
presentations at local, national, and international scientific meetings and publication in
high impact journals. Target audiences will include public health and clinical communities
with an interest in nutrition and cardiovascular disease. Feedback will be incorporated and
used to improve public health messages and key areas for future research will be defined. The
PIs will network among opinion leaders to increase awareness and participate directly in the
development of future guidelines.
SIGNIFICANCE The proposed project will aid in knowledge translation related to the role of
whole grain oats and oat fiber as add-on therapy in the primary and secondary prevention of
cardiovascular disease, strengthening the evidence-base for guidelines development in the
U.S., Canada, Europe, and beyond and improving health outcomes, by educating healthcare
providers and patients, stimulating industry innovation, and guiding future research design.
REFERENCES
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