Meal Timing, Genetics and Weight Loss

Obesity Clinical Trial

— ONTIME  

Official title:

Meal Timing, Genetics and Weight Loss in a Mediterranean Population

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02829619
• Other study ID #: R01DK105072-1
• Secondary ID: R01DK105072
• Status: Recruiting
• Start date: January 1, 2008
• Est. completion date: June 2032

Study information

• Verified date: May 2024
• Source: Universidad de Murcia
• Contact: Marta Garaulet, PHD
• Phone: +34-678996368
• Email: garaulet[@]um.es
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 5788
• Est. completion date: June 2032
• Est. primary completion date: June 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Obesity
• Weight Loss

Locations

Country	Name	City	State
Spain	University of Murcia	Murcia

Sponsors (1)

Lead Sponsor	Collaborator
Universidad de Murcia

Country where clinical trial is conducted

Spain, 

References & Publications (30)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. Erratum In: J Am Diet Assoc. 2011 Apr;111(4):626. — View 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. — View 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. Erratum In: Int J Obes (Lond). 2013 Apr;37(4):624. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

* Note: There are 30 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total weight loss	Body weight will be measured in barefoot wearing light clothes, with a digital scale to the nearest 0.1 kg, at the same time each day.	weekly, during the 28 weeks of treatment
Primary	Long term weight loss maintenance	Body weight will be measured in barefoot wearing light clothes, with a digital scale to the nearest 0.1 kg.	once at least one year after ending the treatment
Secondary	Food timing	Timing of breakfast, lunch and dinner	at baseline
Secondary	Sleep timing	Habitual sleep timing is estimated using a self-reported questionnaire.	at baseline
Secondary	Siesta timing questionnaire	Habitual siesta timing is estimated using a self-reported questionnaire.	at baseline
Secondary	Individual chronotype questionnaire	With the Morning and Eveningness Questionnaire (MEQ)	at baseline
Secondary	Food habits questionnaire	Variety of food groups is assessed by at 24h recall the day before starting the intervention and by a a seven days dietary record during the intervention. The number of different food items per day will be counted to assess variety of food	at baseline
Secondary	Total energy intake dietary questionnaire	by at 24h recall the day before starting the intervention and by a a seven days dietary record during the intervention. Daily energy intake will be calculated	at baseline
Secondary	Macronutrient distribution dietary questionnaire	by at 24h recall the day before starting the intervention and by a a seven days dietary record during the intervention. Macronutrient (% from total calories of the diet) and (grams) will be calculated	at baseline
Secondary	Glycemic Index questionnaire	by at 24h recall the day before starting the intervention and by a a seven days dietary record during the intervention. The glycemic index will be calculated by using different composition tables	at baseline
Secondary	Barriers to Weight Loss checklist	A questionnaire will be complete by the participants. The test consisted of 29 questions classified into seven sections: meal recording; weight control and weekly interviews; eating habits; portion size; food and drink choice; way of eating; and other obstacles to weight loss. There are were three possible responses (never 0, sometimes 1, very often 2) to those questions that represented barriers to losing weight, such as ''Have you lost your motivation?'' or ''Do you have binges?'' Questions that represented aids to weight loss, such as ''Do you accurately measure your portions?'' or ''Is absolutely everything written down?'' applied the same score (0 to 2) but with negative signs. A final ''Barriers to Weight Loss'' score is calculated by adding every answer's score for each patient.	at baseline
Secondary	Emotional eating questionnaire	The EEQ (Emotional eating Questionnaire) will be used extent emotions affect eating behaviour. . All the questions had four possible replies: 1) Never, 2) Sometimes; 3) Generally and 4) Always. Each reply was given a score of 1 to 4, the lower the score, the healthier the behaviour. For the clinical practice subjects are classified in four groups attending to the score obtained. Score between 0-5: non-emotional eater. Score between 6-10: low emotional eater. Score between 11-20: emotional eater. Score between 21-30: very emotional eater.	at baseline
Secondary	Physical activity questionnaire	by the IPAQ (international Physical Activity Questionnaire)	at baseline
Secondary	Mediterranean Diet Score questionnaire	By the questionnaire developed by Antonia Trichopoulou, M.D., Tina Costacou, Ph.D., Christina Bamia, Ph.D., and Dimitrios Trichopoulos, M.D.; N Engl J Med 2003; 348:2599-2608June 26, 2003DOI: 10.1056/NEJMoa025039	at baseline
Secondary	Glucose tolerance	either by meal test or by glucose tolerance test	from 1 year to 3 years after weight loss treatment
Secondary	Daily rhythms of wrist temperature	7 day-record of wrist temperature by wrist temperature sensors.	from 3 months to 3 years after weight loss treatment
Secondary	Daily rhythms of activity	7 day-record of activity by actiwatch	from 3 months to 3 years after weight loss treatment
Secondary	Daily rhythms of autonomus system by ambulatory electrocardiography	7 days of ambulatory electrocardiography	from 3 months to 3 years after weight loss treatment
Secondary	Glucose	Fasting glucose	at baseline
Secondary	Insulin	Fasting insulin	at baseline