Thymol on Netrin-1 on Obese Patients


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.

Full Title of Study: “Thymol Administration Effects on Netrin-1 Serum Concentration on Obese Patients”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: December 15, 2022

Detailed 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.


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

Arms, Groups and Cohorts

  • Experimental: Group A
    • Thymol
  • Placebo Comparator: Group B
    • Calcined magnesia

Clinical Trial Outcome Measures

Primary Measures

  • Netrin-1
    • Time Frame: Change from baseline netrin-1 at 90 days
    • Enzyme-Linked ImmunoSorbent Assay

Secondary Measures

  • IL-6
    • Time Frame: Change from baseline IL-6 at 90 days
    • Enzyme-Linked ImmunoSorbent Assay
  • Adiponectin
    • Time Frame: Change from baseline adiponectin at 90 days
    • Enzyme-Linked ImmunoSorbent Assay
  • Ultrasensitive C-reactive protein
    • Time Frame: Change from baseline hs-PCR at 90 days
    • Enzyme-Linked ImmunoSorbent Assay

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 35 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Centro Universitario de Ciencias de la Salud, Mexico
  • Provider of Information About this Clinical Study
    • Principal Investigator: Maria Guadalupe Ramos Zavala, Clinical Professor – Centro Universitario de Ciencias de la Salud, Mexico
  • Overall Official(s)
    • Maria G Ramos-Zavala, PhD, Study Chair, Centro Universitario de Ciencias de la Salud, Mexico
  • Overall Contact(s)
    • Maria G Ramos-Zavala, PhD, 3339523367,


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