Randomized, Double-Blind, Crossover Trial Comparing Low-Glycemic Index Functional and Conventional Wholegrain...

Mild fasting hypertriglyceridemia is often accompanied by early insulin resistance and atherogenic dyslipidemia, making it an attractive target for pragmatic dietary prevention. This trial aims to determine whether substituting common cereal-based staples with functional low-glycemic index (low-GI) products improves the triglyceride-glucose (TyG) index in adults with fasting triglycerides >150 mg/dL. The GLOW study is an exploratory, randomized, double-blind, single-center crossover trial. Adults aged ≥18 years with fasting triglycerides >150 mg/dL and body mass index ≤30 kg/m² will be enrolled. Participants will follow a stabilized Mediterranean-style diet and will complete two 28-day intervention periods in random sequence: (i) functional low-GI Altograno^® pasta, pizza base and flatbread; and (ii) conventional standard wholegrain products. Intervention periods will be separated by a 28-day washout. Study foods will be consumed as fixed daily substitutions of usual staple servings (one bread portion and one pasta or pizza portion). The primary endpoint is the between-intervention difference in TyG response over each period, defined as the period-specific change from the corresponding period baseline to the end-of-period assessment. The primary analysis will compare end-of-period TyG between interventions while adjusting for the period-specific baseline value. Secondary endpoints include fasting triglycerides and glucose, atherogenic lipoproteins (non-high-density lipoprotein cholesterol and apolipoprotein B), inflammation (high-sensitivity C-reactive protein), endothelial reactivity assessed with the Endocheck^®/Vicorder^® system, and food acceptability. Safety endpoints include adverse event recording. Treatment effects will be estimated using linear mixed-effects models accounting for treatment, period and sequence, with prespecified carryover sensitivity analyses. A total of 40 participants will be recruited to generate feasibility data and effect size estimates. This protocol will provide crossover evidence on whether pragmatic, product-level low-GI staple substitution improves TyG and related cardiometabolic and vascular biomarkers in adults with suboptimal triglyceridemia, informing larger trials. Trial registration: ClinicalTrials.gov NCT07198789.