Thymol on Netrin-1 on Obese Patients

NCT ID: NCT05427721

Last Updated: 2022-06-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-04-01

Study Completion Date

2022-12-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Inflammatory Response Obesity

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Clinical trial
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
Capsules with the same characteristics (smell, color, taste). Random assignment.

Study Groups

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Group A

Thymol

Group Type EXPERIMENTAL

Thymol

Intervention Type DRUG

200 mg each 8 hours for 90 days

Group B

Calcined magnesia

Group Type PLACEBO_COMPARATOR

Thymol

Intervention Type DRUG

200 mg each 8 hours for 90 days

Interventions

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Thymol

200 mg each 8 hours for 90 days

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

35 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Centro Universitario de Ciencias de la Salud, Mexico

OTHER

Sponsor Role lead

Responsible Party

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Maria Guadalupe Ramos Zavala

Clinical Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Maria G Ramos-Zavala, PhD

Role: STUDY_CHAIR

Centro Universitario de Ciencias de la Salud, Mexico

Locations

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INTEC, CUCS, Universidad de Guadalajara

Guadalajara, Jalisco, Mexico

Site Status RECRUITING

Countries

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Mexico

Central Contacts

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Maria G Ramos-Zavala, PhD

Role: CONTACT

3339523367

Jesus J Garcia-Galindo, MD

Role: CONTACT

3325828575

Facility Contacts

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Maria G Ramos-Zavala, PhD

Role: primary

3339533367

Jesus J Garcia-Galindo, MD

Role: backup

3325828575

References

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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.

Reference Type BACKGROUND
PMID: 30067159 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27166942 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23303904 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23223452 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21982709 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17681149 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30532735 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28694777 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24507296 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28911561 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12092740 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29785774 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24372823 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25384116 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26007642 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26680107 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24175857 (View on PubMed)

Other Identifiers

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20-131

Identifier Type: REGISTRY

Identifier Source: secondary_id

CI-01621

Identifier Type: -

Identifier Source: org_study_id

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