Metformin and Systemic Inflammation in HIV (Metfo)

Metformin Administration Effect Over Systemic Inflammation Serum Markers in HIV Positive Prediabetic Patients

The purposes of this study are to find out if: metformin can be combined with anti-HIV drugs to reduce systemic inflammation measured by the determination of cytokines and other series of serum markers. To determine if the concomitant administration of metformin with TARA improves the immune function on the CD4 T cell count and its relation with the CD8 T cells, during the treatment and after its interruption.

To this end, in the present study, patients with prediabetes (who meet the fasting impaired glucose criteria) will be identified and treated with metformin or placebo for 8 weeks, receiving stable TARA and with a CD4 + level> 200 cells / μL.

40 patients from the HIV Unit of the Civil Hospital of Guadalajara "Fray Antonio Alcalde" will be included in this study and the intervention will last 8 weeks.

Study Overview

• Status: Unknown
• Conditions: PreDiabetes; HIV-1-infection
• Intervention / Treatment: Drug: Metformin Hydrochloride 850 MG; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • Hospital Civil de Guadalajara

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Both sexes,
• Age ≥18 years of age
• With a diagnosis of HIV-1 infection,
• That they are receiving TARE for at least 12 months (time necessary to establish a stable reservoir),
• Patients with undetectable viral load (<40 copies / mL) for at least 12 months,
• Have a CD4 + level> 200 cells / μL,
• That they do not have a diagnosis of co-infection with HCV or HBV,
• Patients who do not have a severe alcohol intake (<21 glasses / week in men and <14 glasses / week in women),
• Patients who do not use drugs during the last 90 days prior to the screening visit, or during the study,
• Who wish to participate voluntarily in the study and give their written consent.

Exclusion Criteria:

• Individuals with a known hypersensitivity / allergy to metformin.
• Patients with contraindications to the use of metformin *.
• Individuals who are actively involved in an experimental therapy study or who have received experimental therapy in the last 6 months.
• People suffering from stage IV-V chronic kidney disease, uncontrolled heart failure or active infections.
• Individuals with diabetes mellitus (according to the criteria of the American Diabetes Association *).
• Patients with indication for the use of statins, aspirin or immunomodulators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metformin Experimental Arm; Metformin 850mg/12 hours, oral, 8 weeks	Drug: Metformin Hydrochloride 850 MG; 8 weeks tratment with oral metformin
Placebo Comparator: Placebo Comparator Arm; Placebo pills/12hours, oral, 8 weeks	Other: Placebo; 8 weeks tratment with oral placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantification of proinflammatory cytokines serum levels by Cytometric Bead Array in prediabetic HIV positive patients after 8 weeks treatment with Metformin	Serum levels of proinflammatory cytokines will be quantify by flow cytometry using a Cytometric Bead Array. The cytokine panel to be messured will be as follows: IL-1beta; IFN-alpha2; IFN-gamma; TNF-alpha; MCP-1; IL-6; IL-8; IL-10; IL-12p70; IL-17A; IL-18; IL-23; IL-33 These cytokines will be quantify in prediabetic HIV positive patients after 8 weeks treatment with Metformin	Basal - 8 weeks

Collaborators and Investigators

• Sponsor: Hospital Civil de Guadalajara

Publications and helpful links

General Publications

• Slim J, Saling CF. A Review of Management of Inflammation in the HIV Population. Biomed Res Int. 2016;2016:3420638. doi: 10.1155/2016/3420638. Epub 2016 Sep 27.
• Arafath S, Campbell T, Yusuff J, Sharma R. Prevalence of and Risk Factors for Prediabetes in Patients Infected With HIV. Diabetes Spectr. 2018 May;31(2):139-143. doi: 10.2337/ds17-0009.
• Nou E, Lo J, Grinspoon SK. Inflammation, immune activation, and cardiovascular disease in HIV. AIDS. 2016 Jun 19;30(10):1495-509. doi: 10.1097/QAD.0000000000001109.
• Saisho Y. Metformin and Inflammation: Its Potential Beyond Glucose-lowering Effect. Endocr Metab Immune Disord Drug Targets. 2015;15(3):196-205. doi: 10.2174/1871530315666150316124019.

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2018
• Primary Completion (Anticipated): December 20, 2019
• Study Completion (Anticipated): January 8, 2020

Study Registration Dates

• First Submitted: December 10, 2018
• First Submitted That Met QC Criteria: December 11, 2018
• First Posted (Actual): December 12, 2018

Study Record Updates

• Last Update Posted (Actual): December 19, 2019
• Last Update Submitted That Met QC Criteria: December 17, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: 114/18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Data from participants will be available upon reasonable request
• IPD Sharing Time Frame: Basal - 8 weeks
• IPD Sharing Supporting Information Type: Study Protocol; Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No