NCT07324044

Chrono-ALIGN: A Chronotype-Based Chrono-Nutrition Intervention in Post-Bariatric Patients

Chrono-ALIGN Trial: The Impact of Chronotype-Based Chrono-Nutrition on Metabolic Health, Gut Microbiota, Appetite, and Circadian Alignment in Post-Bariatric Surgery Patients: A Randomized Controlled Trial

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 246 (estimated)
• Sponsor: King Saud University · Academic / Other
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

Summary

This randomized controlled trial will evaluate the impact of chrono-nutrition, a dietary approach that aligns meal timing with the body's circadian rhythms, on weight change, metabolic outcomes, appetite, and gut microbiota in post-bariatric surgery patients. A total of 246 adults who underwent sleeve gastrectomy at least six months earlier will be enrolled at King Saud Medical City. Participants will be randomized to receive either standard post-bariatric nutritional care or personalized chrono-nutrition based on individual chronotype. Outcomes include weight change, metabolic biomarkers, dietary behaviors, sleep patterns, and gut microbiota composition. The study aims to determine whether integrating chrono-nutrition into post-bariatric follow-up can enhance metabolic health and improve long-term health.

Detailed description

Bariatric surgery is the most effective treatment for severe obesity and often induces remission of comorbidities. However, up to 50-70% of patients experience weight recurrence and metabolic relapse within four years, suggesting that there must be adjunct strategies to sustain benefits. Circadian biology, the alignment of internal rhythms with behaviors such as eating and sleep, has emerged as a modifiable determinant of weight regulation, glycemic control, appetite, and inflammation. Chrononutrition, characterized by the deliberate scheduling of meals to correspond with circadian physiology, may present an innovative approach for long-term post-bariatric management. Early time-restricted eating (eTRE) has improved weight and metabolic outcomes in non-surgical populations. Post-bariatric patients may additionally benefit through improved hunger/satiety signaling, circadian alignment, favorable microbiota shifts, and possible epigenetic regulation. Despite this promise, randomized controlled evidence in post-bariatric cohorts is lacking. Rationale and Significance This study addresses a major gap by evaluating whether chrononutrition tailored to chronotype improves long-term metabolic, microbial, and behavioral outcomes after bariatric surgery. Findings may reduce weight regain, enhance glycemic control, optimize gut microbiota composition, and offer information about circadian-epigenetic mechanisms. Results could inform future clinical practice guidelines and integrate precision nutrition into bariatric care. Study Aim and Objectives The primary aim is to evaluate the effect of chronotype-based chrononutrition on metabolic, microbial, epigenetic, and behavioral outcomes in post-bariatric patients. Primary Objective: Assess whether chronotype-based meal timing improves weight maintenance, insulin sensitivity, and gut microbiota diversity compared with standard care and generic eTRE. Secondary Objectives: Examine effects on circadian gene expression, DNA methylation and histone modifications, gut hormones (GLP-1, PYY, ghrelin), eating behavior, sleep, mood, and physical activity. Explore microbiota and epigenetic mediation of outcomes. Hypotheses Patients assigned to chrono-nutrition will demonstrate improved weight maintenance, metabolic outcomes, and circadian alignment compared to standard care. Chrononutrition is expected to alter gut microbiota favorably, epigenetic markers, and behavioral outcomes, with greater benefits observed when meal timing matches chronotype. Study Design This is a randomized controlled trial at King Saud Medical City, Riyadh. Adult patients 6 months post-sleeve gastrectomy will be recruited from the bariatric nutrition clinic. Written informed consent is required. Sample Size and Randomization Based on power calculations, 246 participants (82 per group) will be randomized (1:1:1) to: Control Group, standard post-bariatric care without meal timing. eTRE Group, all meals consumed between 8:00 AM-6:00 PM. Chronotype-Based Group: meal timing tailored to chronotype (morning, intermediate, evening). Randomization will be stratified by chronotype. Follow-up visits will occur at baseline, 3, 6, and 12 months. Inclusion Criteria Adults 18-65 years, ≥6 months post-sleeve gastrectomy, BMI 25-40 kg/m², ≥50% excess weight loss, cleared for a regular diet. Exclusion Criteria: Pregnancy, severe psychiatric illness, major unrelated chronic disease, revision bariatric surgery, prior intermittent fasting regimens, or use of medications affecting circadian rhythm. Blinding: Due to the nature of interventions, participants and dietitians cannot be blinded. Laboratory staff and statisticians will remain blinded to group allocation. Assessments: Anthropometry: weight, BMI, %EWL, waist circumference, bioimpedance body composition. Biochemical markers: fasting glucose, insulin (HOMA-IR),HgbA1c, lipids, CRP, IL-6, TNF-α, leptin, adiponectin, ghrelin, GLP-1, PYY, cortisol, and vitamin D. Gut microbiota: stool samples analyzed via 16S rRNA sequencing; SCFAs measured with GC-MS; bile acids via LC-MS. Epigenetics: blood samples analyzed for DNA methylation (CLOCK, BMAL1, PER2, CRY1), histone modifications, and circadian gene expression (qRT-PCR). Behavioral outcomes: validated questionnaires for sleep (PSQI), mood (BDI, GAD-7), and eating behavior (TFEQ, VAS appetite scores). Physical activity and sleep will also be objectively measured with actigraphy/wearable devices. Dietary Habits: will be measured using Dietary Habit Questionnaire Data Collection Timeline Baseline (6 months post-surgery), then follow-ups at 3, 6, and 12 months. Digital logs and wearable devices will track eating and activity behaviors continuously. Statistical Analysis: Primary outcomes will be analyzed with repeated-measures ANOVA and linear mixed models to compare groups over time. Microbiota diversity will be assessed using PERMANOVA and LEfSe analyses. Epigenetic and behavioral outcomes will be tested with ANCOVA and regression models. Mediation and moderation analyses (SEM) will explore pathways linking chrono-nutrition, microbiota, and metabolic outcomes. Intention-to-treat analysis will be performed, with multiple imputation for missing data. Ethics The study follows the Declaration of Helsinki and is approved by the Ethics Committees of King Saud Medical City and King Saud University. Written informed consent is mandatory, and data will be anonymized. Expected Impact: This is the first RCT to test chronotype-based chrono-nutrition in post-bariatric patients. If effective, it could provide a scalable precision nutrition strategy to reduce weight regain, enhance metabolic outcomes, and guide future clinical guidelines.

Conditions

• Obesity (Disorder)
• Morbid Obesity
• Bariatric Sleeve Gastrectomy
• Meal Time
• Chronotype
• Circadian Rhythm

Interventions

Type	Name	Description
BEHAVIORAL	Standard Post-Bariatric Care (Control)	Participants receive routine post-bariatric nutritional care with no prescribed meal-timing window. Dietitians provide standard guidance on protein adequacy (\~60-80 g/day unless otherwise indicated), hydration, and routine micronutrient supplementation per clinic practice. Follow-ups occur at 3, 6, and 12 months; outcomes include body weight, metabolic markers, appetite-related hormones, questionnaires, wearables, and stool samples. This arm controls for the effects of usual care and non-timing dietary counseling.
BEHAVIORAL	Early Time-Restricted Eating (eTRE)	Participants consume all caloric intake within a fixed daytime 10-hour window (08:00-18:00) on ≥6 days/week. Water/unsweetened tea/black coffee are allowed outside the window. Diet composition follows bariatric guidelines (protein \~60-80 g/day, hydration, routine micronutrients). Dietitians provide structured meal-timing plans and problem-solving support; timing logs and wearables document adherence. Assessments at 3, 6, and 12 months mirror the control arm.
BEHAVIORAL	Chronotype-Based Chrono-Nutrition (CB-CN)	Meal timing is personalized to chronotype (morning/intermediate/evening) determined with the Munich Chronotype Questionnaire (MCTQ). Plans target an earlier first meal and completion of the last meal ≥3-4 h before habitual bedtime, with an eating window of \~10 h/day on ≥6 days/week, adjusted to chronotype using stepwise phase-advance strategies where needed. Diet composition follows bariatric guidelines (protein, hydration, micronutrients). Timing logs and wearables track adherence; visits at 3, 6, and 12 months.

Timeline

• Start date: 2026-01-01
• Primary completion: 2027-12-01
• Completion: 2028-12-01
• First posted: 2026-01-07
• Last updated: 2026-01-07

Locations

1 site across 1 country: Saudi Arabia