Thymol on Netrin-1 on Obese Patients

NCT05427721 | Unknown Phase 2 DMC FDA Drug

• 2 other identifiers: CI-0162120-131
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Inflammatory Response; Obesity

Keywords

Netrin-1; Thymol

Outcome Measures

Primary Outcomes (1)

• Netrin-1

  Enzyme-Linked ImmunoSorbent Assay

  Change from baseline netrin-1 at 90 days

Secondary Outcomes (3)

• IL-6

  Change from baseline IL-6 at 90 days

• Adiponectin

  Change from baseline adiponectin at 90 days

• Ultrasensitive C-reactive protein

  Change from baseline hs-PCR at 90 days

Other Outcomes (6)

• Glucose

  Change from baseline glucosa at 90 days

• Insulin Insulina

  Change from baseline insulina at 90 days

• HDL

  Change from baseline HDL at 90 days

Study Arms (2)

Group A

EXPERIMENTAL

Thymol

Drug: Thymol

Group B

PLACEBO COMPARATOR

Calcined magnesia

Drug: Thymol

Interventions

Thymol DRUG

200 mg each 8 hours for 90 days

Group A; Group B

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centro Universitario de Ciencias de la Salud, Mexico: lead

Study Sites (1)

INTEC, CUCS, Universidad de Guadalajara

Guadalajara, Jalisco, 4430, Mexico

RECRUITING

Related Publications (17)

• 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.

  PMID: 30067159 BACKGROUND

• 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.

  PMID: 27166942 BACKGROUND

• 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.

  PMID: 23303904 BACKGROUND

• 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.

  PMID: 23223452 BACKGROUND

• Lee KY, Gesta S, Boucher J, Wang XL, Kahn CR. The differential role of Hif1beta/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.

  PMID: 21982709 BACKGROUND

• Bouhlel MA, Derudas B, Rigamonti E, Dievart 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. doi: 10.1016/j.cmet.2007.06.010.

  PMID: 17681149 BACKGROUND

• 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.

  PMID: 30532735 BACKGROUND

• 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.

  PMID: 28694777 BACKGROUND

• 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.

  PMID: 24507296 BACKGROUND

• 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.

  PMID: 28911561 BACKGROUND

• Kohlert C, Schindler G, Marz RW, Abel G, Brinkhaus B, Derendorf H, Grafe EU, Veit M. Systemic availability and pharmacokinetics of thymol in humans. J Clin Pharmacol. 2002 Jul;42(7):731-7. doi: 10.1177/009127002401102678.

  PMID: 12092740 BACKGROUND

• 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.

  PMID: 29785774 BACKGROUND

• 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.

  PMID: 24372823 BACKGROUND

• 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.

  PMID: 25384116 BACKGROUND

• 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.

  PMID: 26007642 BACKGROUND

• 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.

  PMID: 26680107 BACKGROUND

• 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.

  PMID: 24175857 BACKGROUND

MeSH Terms

Conditions

Obesity

Interventions

Thymol

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Monoterpenes; Terpenes

Study Officials

• Maria G Ramos-Zavala, PhD

  Centro Universitario de Ciencias de la Salud, Mexico

  STUDY CHAIR

Central Study Contacts

Maria G Ramos-Zavala, PhD

CONTACT

3339523367; ramos.zavala.mg@gmail.com

Jesus J Garcia-Galindo, MD

CONTACT

3325828575; dr.jonathangarcia1418@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Capsules with the same characteristics (smell, color, taste). Random assignment.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Model Details: Clinical trial

Study Record Dates

• First Submitted: June 11, 2021
• First Posted: June 22, 2022
• Study Start: April 1, 2022
• Primary Completion: December 15, 2022
• Study Completion: December 30, 2022
• Last Updated: June 22, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)