Thymol on Netrin-1 on Obese Patients

Obesity Clinical Trial

Official title:

Thymol Administration Effects on Netrin-1 Serum Concentration on Obese Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05427721
• Other study ID #: CI-01621
• Secondary ID: 20-131
• Status: Recruiting
• Phase: Phase 2
• Start date: April 1, 2022
• Est. completion date: December 30, 2022

Study information

• Verified date: June 2022
• Source: Centro Universitario de Ciencias de la Salud, Mexico
• Contact: Maria G Ramos-Zavala, PhD
• Phone: 3339523367
• Email: ramos.zavala.mg[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The prevalence of obesity in Mexico is 35.4%, and it is considered a risk factor for the development of diabetes, systemic arterial hypertension and dyslipidemia. Obesity due to the increased distribution and growth of adipose tissue creates a pro-inflammatory state induced by molecules secreted by the adipocytes themselves. Netrin-1 is a cell migration protein, which directs the recruitment, migration and entrapment of macrophages in different tissues, within adipose tissue the entrapment of macrophages induces the release of pro-inflammatory cytokines, which increase the secretion of pro-inflammatory adipokines. It has been found in high concentration in patients with obesity, insulin resistance and type 2 diabetes. Thymol is a phytopharmaceutical derived from oregano oil that has shown powerful anti-inflammatory and antioxidant effects through the stimulation of PPAR-gamma, adiponectin and inhibition of the NF-κB pathway mediated by the JNK pathway, pathways in which netrin-1 is involved in macrophage entrapment and recruitment.

Description:

Objective: To evaluate the effect of thymol administration on the serum concentration of netrin-1 in obese subjects.

Material and methods: this is a randomized, double-blind, placebo-controlled clinical trial design.

Inclusion criteria:

1. - Subjects between 18 and 35 years old.

2. - Subjects with BMI ≥ 30.0 and ≤35.0.

3. - Subjects with systolic blood pressure less than 135 mmHg.

4. - Subjects with diastolic blood pressure less than 85 mmHg.

5. - Voluntary acceptance and signing of the informed consent. These patients will be randomly assigned to two groups, one will have the intervention with thymol 200 mg every 8 hours for 90 days while the other will have placebo with Mg 200 mg every 8 hours for 90 days.

Statistical analysis: quantitative variables: means and standard deviation. Qualitative variables: frequencies and percentages. In the comparison according to the serum level of netrin-1 between the two groups after the intervention: t student for quantitative variables, Chi square for qualitative variables. Statistical significance p equal to or less than 0.05.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 30, 2022
• Est. primary completion date: December 15, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

• Subjects between 18 and 35 years old.

• BMI = 30.0 and =35.0

• Systolic blood pressure less than 135 mmHg.

• Diastolic blood pressure less than 85 mmHg.

Exclusion Criteria:

• Subjects who are known to have a diagnosis, receive treatment, or are observed with:

• Rheumatological and / or thyroid disease.

• Chronic kidney disease and / or CKD-EPI glomerular filtration rate less than 60 ml / min / 1.72m2.

• Innate alterations of metabolism.

• Elevation of transaminases 2 times higher than normal.

• Total cholesterol greater than 250 mg / dl.

• Triglycerides greater than 300 mg / dl.

• Subjects presenting with acute illness, hospitalization, or drug treatment presented in the last 12 weeks prior to the study selection visit.

• Subjects with symptoms consistent with the definition of a probable case of COVID-19, as well as any subject with a diagnosis of COVID-19.

• Subjects who have had blood transfusions in the last 3 months.

• Regular smokers.

• Pregnant or lactating women.

• Women with a desire for pregnancy or who do not have a double barrier or progestin-only contraceptive method.

Related Conditions & MeSH terms

• Inflammatory Response
• Obesity

Intervention

Drug:
• Thymol
200 mg each 8 hours for 90 days

Locations

Country	Name	City	State
Mexico	INTEC, CUCS, Universidad de Guadalajara	Guadalajara	Jalisco

Sponsors (1)

Lead Sponsor	Collaborator
Centro Universitario de Ciencias de la Salud, Mexico

Country where clinical trial is conducted

Mexico, 

References & Publications (17)

Bouhlel MA, Derudas B, Rigamonti E, Dièvart R, Brozek J, Haulon S, Zawadzki C, Jude B, Torpier G, Marx N, Staels B, Chinetti-Gbaguidi G. PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties. Cell Metab. 2007 Aug;6(2):137-43. — View Citation

Hammarstedt A, Gogg S, Hedjazifar S, Nerstedt A, Smith U. Impaired Adipogenesis and Dysfunctional Adipose Tissue in Human Hypertrophic Obesity. Physiol Rev. 2018 Oct 1;98(4):1911-1941. doi: 10.1152/physrev.00034.2017. Review. — View Citation

Han MS, Jung DY, Morel C, Lakhani SA, Kim JK, Flavell RA, Davis RJ. JNK expression by macrophages promotes obesity-induced insulin resistance and inflammation. Science. 2013 Jan 11;339(6116):218-22. doi: 10.1126/science.1227568. Epub 2012 Dec 6. — View Citation

Haque MR, Ansari SH, Najmi AK, Ahmad MA. Monoterpene phenolic compound thymol prevents high fat diet induced obesity in murine model. Toxicol Mech Methods. 2014 Feb;24(2):116-23. doi: 10.3109/15376516.2013.861888. Epub 2013 Dec 5. — View Citation

Kohlert C, Schindler G, März RW, Abel G, Brinkhaus B, Derendorf H, Gräfe EU, Veit M. Systemic availability and pharmacokinetics of thymol in humans. J Clin Pharmacol. 2002 Jul;42(7):731-7. — View Citation

Lee KY, Gesta S, Boucher J, Wang XL, Kahn CR. The differential role of Hif1ß/Arnt and the hypoxic response in adipose function, fibrosis, and inflammation. Cell Metab. 2011 Oct 5;14(4):491-503. doi: 10.1016/j.cmet.2011.08.006. — View Citation

Marzouk T, Barakat R, Ragab A, Badria F, Badawy A. Lavender-thymol as a new topical aromatherapy preparation for episiotomy: A randomised clinical trial. J Obstet Gynaecol. 2015;35(5):472-5. doi: 10.3109/01443615.2014.970522. — View Citation

Nagoor Meeran MF, Javed H, Al Taee H, Azimullah S, Ojha SK. Pharmacological Properties and Molecular Mechanisms of Thymol: Prospects for Its Therapeutic Potential and Pharmaceutical Development. Front Pharmacol. 2017 Jun 26;8:380. doi: 10.3389/fphar.2017.00380. eCollection 2017. Review. — View Citation

Nieddu M, Rassu G, Boatto G, Bosi P, Trevisi P, Giunchedi P, Carta A, Gavini E. Improvement of thymol properties by complexation with cyclodextrins: in vitro and in vivo studies. Carbohydr Polym. 2014 Feb 15;102:393-9. doi: 10.1016/j.carbpol.2013.10.084. Epub 2013 Nov 20. — View Citation

Paul S, Baranya Shrikrishna S, Suman E, Shenoy R, Rao A. Effect of fluoride varnish and chlorhexidine-thymol varnish on mutans streptococci levels in human dental plaque: a double-blinded randomized controlled trial. Int J Paediatr Dent. 2014 Nov;24(6):399-408. doi: 10.1111/ipd.12085. Epub 2013 Dec 25. — View Citation

Salehi B, Mishra AP, Shukla I, Sharifi-Rad M, Contreras MDM, Segura-Carretero A, Fathi H, Nasrabadi NN, Kobarfard F, Sharifi-Rad J. Thymol, thyme, and other plant sources: Health and potential uses. Phytother Res. 2018 Sep;32(9):1688-1706. doi: 10.1002/ptr.6109. Epub 2018 May 22. Review. — View Citation

Saravanan S, Pari L. Protective effect of thymol on high fat diet induced diabetic nephropathy in C57BL/6J mice. Chem Biol Interact. 2016 Feb 5;245:1-11. doi: 10.1016/j.cbi.2015.11.033. Epub 2015 Dec 8. — View Citation

Saravanan S, Pari L. Role of thymol on hyperglycemia and hyperlipidemia in high fat diet-induced type 2 diabetic C57BL/6J mice. Eur J Pharmacol. 2015 Aug 15;761:279-87. doi: 10.1016/j.ejphar.2015.05.034. Epub 2015 May 22. — View Citation

Stern JH, Rutkowski JM, Scherer PE. Adiponectin, Leptin, and Fatty Acids in the Maintenance of Metabolic Homeostasis through Adipose Tissue Crosstalk. Cell Metab. 2016 May 10;23(5):770-84. doi: 10.1016/j.cmet.2016.04.011. Review. — View Citation

Trayhurn P. Hypoxia and adipose tissue function and dysfunction in obesity. Physiol Rev. 2013 Jan;93(1):1-21. doi: 10.1152/physrev.00017.2012. Review. — View Citation

Yim J, Kim G, Lee BW, Kang ES, Cha BS, Kim JH, Cho JW, Lee SG, Lee YH. Relationship Between Circulating Netrin-1 Concentration, Impaired Fasting Glucose, and Newly Diagnosed Type 2 Diabetes. Front Endocrinol (Lausanne). 2018 Nov 23;9:691. doi: 10.3389/fendo.2018.00691. eCollection 2018. — View Citation

Yu YM, Chao TY, Chang WC, Chang MJ, Lee MF. Thymol reduces oxidative stress, aortic intimal thickening, and inflammation-related gene expression in hyperlipidemic rabbits. J Food Drug Anal. 2016 Jul;24(3):556-563. doi: 10.1016/j.jfda.2016.02.004. Epub 2016 Apr 12. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Glucose	Colorimetry	Change from baseline glucosa at 90 days
Other	Insulin Insulina	Colorimetry	Change from baseline insulina at 90 days
Other	HDL	Colorimetry	Change from baseline HDL at 90 days
Other	LDL	Colorimetry	Change from baseline LDL at 90 days
Other	% visceral fat	Bioelectrical impedance analysis	Change from baseline % visceral fat at 90 days
Other	Abdominal Circumference	Centimeters	Change from baseline abdominal circumference at 90 days
Primary	Netrin-1	Enzyme-Linked ImmunoSorbent Assay	Change from baseline netrin-1 at 90 days
Secondary	IL-6	Enzyme-Linked ImmunoSorbent Assay	Change from baseline IL-6 at 90 days
Secondary	Adiponectin	Enzyme-Linked ImmunoSorbent Assay	Change from baseline adiponectin at 90 days
Secondary	Ultrasensitive C-reactive protein	Enzyme-Linked ImmunoSorbent Assay	Change from baseline hs-PCR at 90 days