Clinical trial NCT02829619: Meal Timing, Genetics and Weight Loss
Official title: Meal Timing, Genetics and Weight Loss in a Mediterranean Population
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Obesity
Keywords: Obesity
Nutrigenetics
Food Timing
Weight loss
Lead sponsor: Universidad de Murcia
Sponsor class: OTHER
First posted: 2016-07-12
Enrollment: 5788
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: All participants are voluntarily attending five weight loss clinics in Spain for dietetic and behavioral treatment based upon the principles of a Mediterranean diet . All participants are from the Spanish city of Murcia, located on the Southeast coast of the Mediterranean Sea.

Brief summary: Meal times differ from culture to culture. These differences may influence energy regulation and, consequently, body weight. Current studies support the notion that not only "what" but also "when" the investigators eat may have a significant role in obesity treatment. Recently, it has been shown that eating the main meal of the day, lunch in Spain, late in the day is predictive of difficulty in weight loss and decreased insulin sensitivity. This project aims to study in a Mediterranean population the potential influence of genetics and food timing on obesity, metabolic syndrome and weight loss.

Detailed description: Meal times differ from culture to culture. These differences may influence energy regulation and, consequently, body weight. Current studies support the notion that not only "what" but also "when" the investigators eat may have a significant role in obesity treatment. Recently, it has been shown that eating the main meal of the day, lunch in Spain, late in the day is predictive of difficulty in weight loss and decreased insulin sensitivity. Furthermore, it has been shown that eating late at night when plasma melatonin concentrations are elevated, impairs glucose tolerance, particularly in MTNR1B risk allele carriers.

The main objective is to identify the mechanisms underlying the association between the timing of food intake, obesity and metabolic syndrome (MetS) in order to design effective weight loss therapies. The long-term goal is to determine the potential impact of more European, i.e., earlier meal timing on obesity, MetS and weight loss.

The challenge for the society is to develop evidence-based dietary interventions incorporating meal timing and genotype to combat the epidemic of obesity and MetS.

These goals will be achieved through three specific approaches:

* Epidemiological (observational study) (Aim 1): To assess in an obese population (n=5000) who will follow a weight loss program if clock-related (CLOCK, PER2, CRY, etc.) and melatonin-related variants (MTNR1B) interact with the timing of food intake to determine weight loss effectiveness and MetS features.
* Interventional (randomized controlled trials) (Aim 2): To determine the internal mechanisms of energy balance and circadian system implicated in the differential effects of food timing (lunch) on weight loss, MetS alterations and the intestinal microbiota (n=25), and to study the potential interaction between meal timing (dinner) and genetic variants MTNR1B for glucose tolerance in obese women (n=100).

Eligibility criteria: Inclusion Criteria:

* Body Mass Index: \>25 kg/m2
* Age: \>18 years of age
* Caucasian

Exclusion Criteria:

* Receiving treatment with thermogenic, lipogenic, or contraceptive drugs
* Diabetes mellitus, chronic renal failure, hepatic diseases, or cancer diagnosis
* bulimia diagnosis, prone to binge eating
* undergoing treatment with anxiolytic or antidepressant drugs

Primary outcomes:
measure: Total weight loss
timeFrame: weekly, during the 28 weeks of treatment
measure: Long term weight loss maintenance
timeFrame: once at least one year after ending the treatment
Secondary outcomes:
measure: Food timing
timeFrame: at baseline
measure: Sleep timing
timeFrame: at baseline
measure: Siesta timing questionnaire
timeFrame: at baseline
measure: Individual chronotype questionnaire
timeFrame: at baseline
measure: Food habits questionnaire
timeFrame: at baseline
measure: Total energy intake dietary questionnaire
timeFrame: at baseline
measure: Macronutrient distribution dietary questionnaire
timeFrame: at baseline
measure: Glycemic Index questionnaire
timeFrame: at baseline
measure: Barriers to Weight Loss checklist
timeFrame: at baseline
measure: Emotional eating questionnaire
timeFrame: at baseline
measure: Physical activity questionnaire
timeFrame: at baseline
measure: Mediterranean Diet Score questionnaire
timeFrame: at baseline
measure: Glucose tolerance
timeFrame: from 1 year to 3 years after weight loss treatment
measure: Daily rhythms of wrist temperature
timeFrame: from 3 months to 3 years after weight loss treatment
measure: Daily rhythms of activity
timeFrame: from 3 months to 3 years after weight loss treatment
measure: Daily rhythms of autonomus system by ambulatory electrocardiography
timeFrame: from 3 months to 3 years after weight loss treatment
measure: Glucose
timeFrame: at baseline
measure: Insulin
timeFrame: at baseline
Other outcomes:
Locations:
city: Murcia
country: Spain
facility: University of Murcia
Study officials:
affiliation: Universidad de Murcia
name: Marta Garaulet, PHD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Garaulet M, Vera B, Bonnet-Rubio G, Gomez-Abellan P, Lee YC, Ordovas JM. Lunch eating predicts weight-loss effectiveness in carriers of the common allele at PERILIPIN1: the ONTIME (Obesity, Nutrigenetics, Timing, Mediterranean) study. Am J Clin Nutr. 2016 Oct;104(4):1160-1166. doi: 10.3945/ajcn.116.134528. Epub 2016 Sep 14.
citation: Gomez-Santos C, Saura CB, Lucas JA, Castell P, Madrid JA, Garaulet M. Menopause status is associated with circadian- and sleep-related alterations. Menopause. 2016 Jun;23(6):682-90. doi: 10.1097/GME.0000000000000612.
citation: Corbalan-Tutau MD, Gomez-Abellan P, Madrid JA, Canteras M, Ordovas JM, Garaulet M. Toward a chronobiological characterization of obesity and metabolic syndrome in clinical practice. Clin Nutr. 2015 Jun;34(3):477-83. doi: 10.1016/j.clnu.2014.05.007. Epub 2014 May 28.
citation: Lopez-Guimera G, Dashti HS, Smith CE, Sanchez-Carracedo D, Ordovas JM, Garaulet M. CLOCK 3111 T/C SNP interacts with emotional eating behavior for weight-loss in a Mediterranean population. PLoS One. 2014 Jun 6;9(6):e99152. doi: 10.1371/journal.pone.0099152. eCollection 2014.
citation: Dashti HS, Smith CE, Lee YC, Parnell LD, Lai CQ, Arnett DK, Ordovas JM, Garaulet M. CRY1 circadian gene variant interacts with carbohydrate intake for insulin resistance in two independent populations: Mediterranean and North American. Chronobiol Int. 2014 Jun;31(5):660-7. doi: 10.3109/07420528.2014.886587. Epub 2014 Feb 18.
citation: Bandin C, Martinez-Nicolas A, Ordovas JM, Madrid JA, Garaulet M. Circadian rhythmicity as a predictor of weight-loss effectiveness. Int J Obes (Lond). 2014 Aug;38(8):1083-8. doi: 10.1038/ijo.2013.211. Epub 2013 Nov 15.
citation: Garaulet M, Smith CE, Gomez-Abellan P, Ordovas-Montanes M, Lee YC, Parnell LD, Arnett DK, Ordovas JM. REV-ERB-ALPHA circadian gene variant associates with obesity in two independent populations: Mediterranean and North American. Mol Nutr Food Res. 2014 Apr;58(4):821-9. doi: 10.1002/mnfr.201300361. Epub 2013 Oct 31.
citation: Garaulet M, Gomez-Abellan P. Chronobiology and obesity. Nutr Hosp. 2013 Sep;28 Suppl 5:114-20. doi: 10.3305/nh.2013.28.sup5.6926.
citation: Morales-Falo EM, Sanchez-Moreno C, Esteban A, Alburquerque JJ, Garaulet M. [Quality of the diet "before and during" a weight loss treatment based on Mediterranean Diet; behavioural therapy and nutritional education]. Nutr Hosp. 2013 Jul-Aug;28(4):980-7. doi: 10.3305/nh.2013.28.4.6665. Spanish.
citation: Garaulet M, Gomez-Abellan P, Alburquerque-Bejar JJ, Lee YC, Ordovas JM, Scheer FA. Timing of food intake predicts weight loss effectiveness. Int J Obes (Lond). 2013 Apr;37(4):604-11. doi: 10.1038/ijo.2012.229. Epub 2013 Jan 29.
citation: Bandin C, Martinez-Nicolas A, Ordovas JM, Ros Lucas JA, Castell P, Silvente T, Madrid JA, Garaulet M. Differences in circadian rhythmicity in CLOCK 3111T/C genetic variants in moderate obese women as assessed by thermometry, actimetry and body position. Int J Obes (Lond). 2013 Aug;37(8):1044-50. doi: 10.1038/ijo.2012.180. Epub 2012 Nov 20.
citation: Milagro FI, Gomez-Abellan P, Campion J, Martinez JA, Ordovas JM, Garaulet M. CLOCK, PER2 and BMAL1 DNA methylation: association with obesity and metabolic syndrome characteristics and monounsaturated fat intake. Chronobiol Int. 2012 Nov;29(9):1180-94. doi: 10.3109/07420528.2012.719967. Epub 2012 Sep 24.
citation: Garaulet M, Canteras M, Morales E, Lopez-Guimera G, Sanchez-Carracedo D, Corbalan-Tutau MD. Validation of a questionnaire on emotional eating for use in cases of obesity: the Emotional Eater Questionnaire (EEQ). Nutr Hosp. 2012 Mar-Apr;27(2):645-51. doi: 10.1590/S0212-16112012000200043.
citation: Corbalan-Tutau D, Madrid JA, Nicolas F, Garaulet M. Daily profile in two circadian markers "melatonin and cortisol" and associations with metabolic syndrome components. Physiol Behav. 2014 Jan 17;123:231-5. doi: 10.1016/j.physbeh.2012.06.005. Epub 2012 Jun 15.
citation: Corbalan-Tutau MD, Madrid JA, Garaulet M. Timing and duration of sleep and meals in obese and normal weight women. Association with increase blood pressure. Appetite. 2012 Aug;59(1):9-16. doi: 10.1016/j.appet.2012.03.015. Epub 2012 Mar 23.
citation: Garaulet M, Esteban Tardido A, Lee YC, Smith CE, Parnell LD, Ordovas JM. SIRT1 and CLOCK 3111T> C combined genotype is associated with evening preference and weight loss resistance in a behavioral therapy treatment for obesity. Int J Obes (Lond). 2012 Nov;36(11):1436-41. doi: 10.1038/ijo.2011.270. Epub 2012 Feb 7.
citation: Garaulet M, Smith CE, Hernandez-Gonzalez T, Lee YC, Ordovas JM. PPARgamma Pro12Ala interacts with fat intake for obesity and weight loss in a behavioural treatment based on the Mediterranean diet. Mol Nutr Food Res. 2011 Dec;55(12):1771-9. doi: 10.1002/mnfr.201100437. Epub 2011 Nov 21.
citation: Corbalan-Tutau MD, Madrid JA, Ordovas JM, Smith CE, Nicolas F, Garaulet M. Differences in daily rhythms of wrist temperature between obese and normal-weight women: associations with metabolic syndrome features. Chronobiol Int. 2011 May;28(5):425-33. doi: 10.3109/07420528.2011.574766.
citation: Smith CE, Ordovas JM, Sanchez-Moreno C, Lee YC, Garaulet M. Apolipoprotein A-II polymorphism: relationships to behavioural and hormonal mediators of obesity. Int J Obes (Lond). 2012 Jan;36(1):130-6. doi: 10.1038/ijo.2011.24. Epub 2011 Mar 8.
citation: Sanchez-Moreno C, Ordovas JM, Smith CE, Baraza JC, Lee YC, Garaulet M. APOA5 gene variation interacts with dietary fat intake to modulate obesity and circulating triglycerides in a Mediterranean population. J Nutr. 2011 Mar;141(3):380-5. doi: 10.3945/jn.110.130344. Epub 2011 Jan 5.
citation: Garaulet M, Corbalan-Tutau MD, Madrid JA, Baraza JC, Parnell LD, Lee YC, Ordovas JM. PERIOD2 variants are associated with abdominal obesity, psycho-behavioral factors, and attrition in the dietary treatment of obesity. J Am Diet Assoc. 2010 Jun;110(6):917-21. doi: 10.1016/j.jada.2010.03.017.
citation: Garaulet M, Corbalan MD, Madrid JA, Morales E, Baraza JC, Lee YC, Ordovas JM. CLOCK gene is implicated in weight reduction in obese patients participating in a dietary programme based on the Mediterranean diet. Int J Obes (Lond). 2010 Mar;34(3):516-23. doi: 10.1038/ijo.2009.255. Epub 2010 Jan 12.
citation: Garaulet M, Lee YC, Shen J, Parnell LD, Arnett DK, Tsai MY, Lai CQ, Ordovas JM. CLOCK genetic variation and metabolic syndrome risk: modulation by monounsaturated fatty acids. Am J Clin Nutr. 2009 Dec;90(6):1466-75. doi: 10.3945/ajcn.2009.27536. Epub 2009 Oct 21.
citation: Gomez-Abellan P, Hernandez-Morante JJ, Lujan JA, Madrid JA, Garaulet M. Clock genes are implicated in the human metabolic syndrome. Int J Obes (Lond). 2008 Jan;32(1):121-8. doi: 10.1038/sj.ijo.0803689. Epub 2007 Jul 24.
citation: Lo MT, Bandin C, Yang HW, Scheer FAJL, Hu K, Garaulet M. CLOCK 3111T/C genetic variant influences the daily rhythm of autonomic nervous function: relevance to body weight control. Int J Obes (Lond). 2018 Feb;42(2):190-197. doi: 10.1038/ijo.2017.168. Epub 2017 Jul 24.
citation: Bonnet G, Gomez-Abellan P, Vera B, Sanchez-Romera JF, Hernandez-Martinez AM, Sookoian S, Pirola CJ, Garaulet M. Serotonin-transporter promoter polymorphism modulates the ability to control food intake: Effect on total weight loss. Mol Nutr Food Res. 2017 Nov;61(11). doi: 10.1002/mnfr.201700494. Epub 2017 Sep 1.
citation: Vera B, Dashti HS, Gomez-Abellan P, Hernandez-Martinez AM, Esteban A, Scheer FAJL, Saxena R, Garaulet M. Modifiable lifestyle behaviors, but not a genetic risk score, associate with metabolic syndrome in evening chronotypes. Sci Rep. 2018 Jan 17;8(1):945. doi: 10.1038/s41598-017-18268-z.
citation: Dashti HS, Gomez-Abellan P, Qian J, Esteban A, Morales E, Scheer FAJL, Garaulet M. Late eating is associated with cardiometabolic risk traits, obesogenic behaviors, and impaired weight loss. Am J Clin Nutr. 2021 Jan 4;113(1):154-161. doi: 10.1093/ajcn/nqaa264.
citation: Garaulet M, Vizmanos B, Muela T, Betancourt-Nunez A, Bonmati-Carrion MA, Vetter C, Dashti HS, Saxena R, Scheer FAJL. Evening types as determined by subjective and objective measures are more emotional eaters. Obesity (Silver Spring). 2023 May;31(5):1192-1203. doi: 10.1002/oby.23749.
citation: Vizmanos B, Cascales AI, Rodriguez-Martin M, Salmeron D, Morales E, Aragon-Alonso A, Scheer FAJL, Garaulet M. Lifestyle mediators of associations among siestas, obesity, and metabolic health. Obesity (Silver Spring). 2023 May;31(5):1227-1239. doi: 10.1002/oby.23765.