Changes in Anthropometric, Biochemical and DNA Damage Parameters After 3-weeks VLCD in Severely Obese Patients

Obesity Clinical Trial

Official title:

Changes in Anthropometric, Biochemical and DNA Damage Parameters After 3-weeks-567-kcal VLCD in Severely Obese Patients With BMI ≥ 35kg/m2

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05007171
• Other study ID #: DNAa3WVLCDiBMI-35/22
• Status: Completed
• Phase: N/A
• Start date: June 14, 2019
• Est. completion date: March 9, 2020

Study information

• Verified date: August 2021
• Source: Special Hospital for Extended Treatment of Duga Resa
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Obesity manifest with inflammation, hyperglycaemia and dyslipidaemia. These conditions disturb redox system by generating excessive reactive oxygen species (ROS) and causing oxidative stress (OS) leading to DNA damage. Very low calorie diet (VLCD) have rapid positive effect on weight loss, glucose homeostasis, inflammation and OS. The aim of study is to test the influence of 3-weeks VLCD on anthropometric, biochemical and genomic parameters in class II and III obesity patients.

Description:

Obesity is a chronic disease associated with chronic inflammation, insulin resistance, dyslipidemia, oxidative stress and increased risk for type 2 diabetes, cardiovascular disease, stroke and multiple cancer types. Oxidative stress can lead to base lesions of DNA which could be detected with alkine comet assay and its version with use of formamidopyrimidine DNA glycosylase-endonuclease enzyme in fresh or frozen small volume samples. Dietary caloric restriction has beneficial effects on insulin sensitivity, inflammation, oxidative stress and DNA repair. Very low calorie diet (VLCD) data are scarce, especially on the changing levels of DNA damage.This study will assess the effect of a three-week VLCD used in Special Hospital for extended treatment of Duga Resa in individuals with BMI ≥ 35kg/m2 on the level of primary and oxidative DNA damage as well as body composition and biochemical parameters.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: March 9, 2020
• Est. primary completion date: March 9, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• body mass index = 35 kg/m2

Exclusion Criteria:

• pregnancy
• actual tumor diseases
• recent diagnostic or treatment exposures to ionizing radiation in the period of one year
• individuals not willing to stay 3 weeks under supervision under full 24 h surveillance from the medical stuff

Related Conditions & MeSH terms

• DNA Damage
• Obesity
• Weight Loss

Intervention

Device:
• Very low calorie diet
During 3 weeks in hospital patients will eat prepared very low calorie diet composed of 50-60% complex carbohydrates with low carbo-glycemic index, 20-25% proteins and 25-30% fat

Locations

Country	Name	City	State
Croatia	Special Hospital for Extended Treatment of Duga Resa	Duga Resa	City Of Zagreb

Sponsors (3)

Lead Sponsor	Collaborator
Special Hospital for Extended Treatment of Duga Resa	Institute for Medical Research and Occupational Health, University of Zagreb

Country where clinical trial is conducted

Croatia, 

References & Publications (17)

Harper C, Maher J, Grunseit A, Seimon RV, Sainsbury A. Experiences of using very low energy diets for weight loss by people with overweight or obesity: a review of qualitative research. Obes Rev. 2018 Oct;19(10):1412-1423. doi: 10.1111/obr.12715. Epub 2018 Aug 24. Review. — View Citation

Hart RW, Dixit R, Seng J, Turturro A, Leakey JE, Feuers R, Duffy P, Buffington C, Cowan G, Lewis S, Pipkin J, Li SY. Adaptive role of caloric intake on the degenerative disease processes. Toxicol Sci. 1999 Dec;52(2 Suppl):3-12. Review. — View Citation

Heilbronn LK, de Jonge L, Frisard MI, DeLany JP, Larson-Meyer DE, Rood J, Nguyen T, Martin CK, Volaufova J, Most MM, Greenway FL, Smith SR, Deutsch WA, Williamson DA, Ravussin E; Pennington CALERIE Team. Effect of 6-month calorie restriction on biomarkers of longevity, metabolic adaptation, and oxidative stress in overweight individuals: a randomized controlled trial. JAMA. 2006 Apr 5;295(13):1539-48. Erratum in: JAMA. 2006 Jun 7;295(21):2482. — View Citation

Heydari AR, Unnikrishnan A, Lucente LV, Richardson A. Caloric restriction and genomic stability. Nucleic Acids Res. 2007;35(22):7485-96. Epub 2007 Oct 16. Review. — View Citation

Himbert C, Thompson H, Ulrich CM. Effects of Intentional Weight Loss on Markers of Oxidative Stress, DNA Repair and Telomere Length - a Systematic Review. Obes Facts. 2017;10(6):648-665. doi: 10.1159/000479972. Epub 2017 Dec 14. — View Citation

Langie SA, Azqueta A, Collins AR. The comet assay: past, present, and future. Front Genet. 2015 Aug 13;6:266. doi: 10.3389/fgene.2015.00266. eCollection 2015. — View Citation

Milic M, Kišan M, Rogulj D, Radman M, Lovrencic MV, Konjevoda P, Domijan AM. Level of primary DNA damage in the early stage of metabolic syndrome. Mutat Res. 2013 Dec 12;758(1-2):1-5. doi: 10.1016/j.mrgentox.2013.07.013. Epub 2013 Sep 27. — View Citation

Milic M, Ožvald I, Vinkovic Vrcek I, Vucic Lovrencic M, Orešcanin V, Bonassi S, Del Castillo ER. Alkaline comet assay results on fresh and one-year frozen whole blood in small volume without cryo-protection in a group of people with different health status. Mutat Res. 2019 Jul;843:3-10. doi: 10.1016/j.mrgentox.2019.03.009. Epub 2019 Mar 28. — View Citation

Mulligan AA, Luben RN, Bhaniani A, Parry-Smith DJ, O'Connor L, Khawaja AP, Forouhi NG, Khaw KT; EPIC-Norfolk FFQ Study. A new tool for converting food frequency questionnaire data into nutrient and food group values: FETA research methods and availability. BMJ Open. 2014 Mar 27;4(3):e004503. doi: 10.1136/bmjopen-2013-004503. — View Citation

Parretti HM, Jebb SA, Johns DJ, Lewis AL, Christian-Brown AM, Aveyard P. Clinical effectiveness of very-low-energy diets in the management of weight loss: a systematic review and meta-analysis of randomized controlled trials. Obes Rev. 2016 Mar;17(3):225-34. doi: 10.1111/obr.12366. Epub 2016 Jan 18. Review. — View Citation

Portnay GI, O'Brian JT, Bush J, Vagenakis AG, Azizi F, Arky RA, Ingbar SH, Braverman LE. The effect of starvation on the concentration and binding of thyroxine and triiodothyronine in serum and on the response to TRH. J Clin Endocrinol Metab. 1974 Jul;39(1):191-4. — View Citation

Rogulj D, Konjevoda P, Milic M, Mladinic M, Domijan AM. Fatty liver index as an indicator of metabolic syndrome. Clin Biochem. 2012 Jan;45(1-2):68-71. doi: 10.1016/j.clinbiochem.2011.10.014. Epub 2011 Oct 26. — View Citation

Setayesh T, Mišík M, Langie SAS, Godschalk R, Waldherr M, Bauer T, Leitner S, Bichler C, Prager G, Krupitza G, Haslberger A, Knasmüller S. Impact of Weight Loss Strategies on Obesity-Induced DNA Damage. Mol Nutr Food Res. 2019 Sep;63(17):e1900045. doi: 10.1002/mnfr.201900045. Epub 2019 Jun 14. — View Citation

Setayesh T, Nersesyan A, Mišík M, Ferk F, Langie S, Andrade VM, Haslberger A, Knasmüller S. Impact of obesity and overweight on DNA stability: Few facts and many hypotheses. Mutat Res Rev Mutat Res. 2018 Jul - Sep;777:64-91. doi: 10.1016/j.mrrev.2018.07.001. Epub 2018 Jul 11. Review. — View Citation

Snel M, Jonker JT, Hammer S, Kerpershoek G, Lamb HJ, Meinders AE, Pijl H, de Roos A, Romijn JA, Smit JW, Jazet IM. Long-term beneficial effect of a 16-week very low calorie diet on pericardial fat in obese type 2 diabetes mellitus patients. Obesity (Silver Spring). 2012 Aug;20(8):1572-6. doi: 10.1038/oby.2011.390. Epub 2012 Jan 26. — View Citation

Usman M, Volpi EV. DNA damage in obesity: Initiator, promoter and predictor of cancer. Mutat Res Rev Mutat Res. 2018 Oct - Dec;778:23-37. doi: 10.1016/j.mrrev.2018.08.002. Epub 2018 Aug 17. Review. — View Citation

Wlodarczyk M, Nowicka G. Obesity, DNA Damage, and Development of Obesity-Related Diseases. Int J Mol Sci. 2019 Mar 6;20(5). pii: E1146. doi: 10.3390/ijms20051146. Review. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The changes in the body mass index	Body mass index (kg/m2) is calculated by using measured body weight (kg) with measured body height (m)	Baseline, after 3 weeks of VLCD
Primary	The changes in the body fat mass	Body fat mass (kg) assessed with bioelectrical impedance method	Baseline, after 3 weeks of VLCD
Primary	The changes in the skeletal muscle mass	Skeletal muscle mass (kg) assessed with bioelectrical impedance method	Baseline, after 3 weeks of VLCD
Primary	The changes in the percent body fat	Percent body fat (%) assessed with bioelectrical impedance method	Baseline, after 3 weeks of VLCD
Primary	The changes in fasting glucose concentration	Concentration of glucose (mmol/L)	Baseline, after 3 weeks of VLCD
Primary	The changes in urea concentration	Concentration of urea (mmol/L)	Baseline, after 3 weeks of VLCD
Primary	The changes in insulin concentration	Concentration of insulin (mIU/L)	Baseline, after 3 weeks of VLCD
Primary	The changes in HOMA index	HOMA index is calculated according to the formula: glucose (mmol/L) x insulin (mIU/L)/22.5	Baseline, after 3 weeks of VLCD
Primary	The changes in lipid profile	Concentrations of triglycerides (mmo/L), LDL (mmol/L), HDL (mmol/L) cholesterol (mmol/L)	Baseline, after 3 weeks of VLCD
Primary	The changes in inflammation parameters	Concentration of C-reactive protein (mg/L)	Baseline, after 3 weeks of VLCD
Primary	The changes in inflammation parameters	Concentration of total white blood cell count	Baseline, after 3 weeks of VLCD
Secondary	The changes in DNA damage assessed with alkaline comet assay	Values for alkaline comet assay in µm for tale length	Baseline, after 3 weeks of VLCD
Secondary	The changes in DNA damage assessed with alkaline comet assay	Values for alkaline comet assay in % for tale intensity	Baseline, after 3 weeks of VLCD
Secondary	The changes in oxidative DNA damage assessed with FPG comet assay	Values for FPG comet assay in % for tale intensity	Baseline, after 3 weeks of VLCD