Effects of Cannabidiol (CBD) on the Activation of Autophagy and Inflammation Genes, Functional Consequences in Virologically Controlled HIV-infected Patients

NCT05306249 | Completed Phase 2

• 1 other identifier: CHRO-2021-01
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Autophagy and apoptosis are natural cellular mechanisms which consist for the first in a recycling and elimination process of potentially toxic cellular waste, and for the second in a process of cellular suicide when it becomes abnormal and "not" repairable, notably by autophagy. A deficit in autophagic function at the cellular level can lead to chronic inflammation and accelerated cellular senescence. Apoptosis is a beneficial phenomenon because it eliminates abnormal cells that could endanger the organism if it survives (e.g. karyotypic atypia). Uncontrolled, it can be deleterious if apoptosis is hypo or hyperactive.

Conditions

HIV Seropositivity

Keywords

HIV-1; CBD

Outcome Measures

Primary Outcomes (3)

• Percentage of variation in the quantification of the corresponding mRNAs

  Percentage of variation in the quantification of the corresponding mRNAs in the mononuclear cells in the different arms of the study

  Day 0

• Percentage of variation in the quantification of the corresponding mRNAs

  Percentage of variation in the quantification of the corresponding mRNAs in the mononuclear cells in the different arms of the study

  Week 4

• Percentage of variation in the quantification of the corresponding mRNAs

  Percentage of variation in the quantification of the corresponding mRNAs in the mononuclear cells in the different arms of the study

  Week 12

Secondary Outcomes (33)

• Quantifications of the quantities of mRNA in each cell subpopulation

  Day 0

• Quantifications of the quantities of mRNA in each cell subpopulation

  Week 4

• Quantifications of the quantities of mRNA in each cell subpopulation

  Week 12

• Quantification of the Global and targeted methylation (promoters of autophagy genes) of DNA

  Day 0

• Quantification of the Global and targeted methylation (promoters of autophagy genes) of DNA

  Week 4

Study Arms (2)

CBD LGP 50 group

EXPERIMENTAL

Patients will receive CBD LGP 50 at a dose of 1 mg/kg twice a day in the form of oil dispensed through a graduated pipette until the end of week 12.

Drug: CBD LGP 50

Control group

PLACEBO COMPARATOR

Patients will receive the MCT oil placebo without CBD until the end of week 12.

Drug: Placebo

Interventions

CBD LGP 50 DRUG

Patients will receive CBD LGP 50 at a dose of 1 mg/kg twice a day in the form of oil dispensed through a graduated pipette until the end of week 12.

CBD LGP 50 group

Placebo DRUG

Patients will receive the MCT oil placebo without CBD until the end of week 12.

Control group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Patient aged 18 or over at the time of signing the informed consent.
• Adults living with HIV1 not co-infected with HIV2
• Patient not taking recreational drugs including cannabis in the past six months
• Affiliated with social security
• Men or women. Women must not be pregnant or breastfeeding. If they are of childbearing potential, they should receive active contraception.
• Be able to give informed written consent.

You may not qualify if:

• Women who are pregnant or breastfeeding, or planning to become pregnant or breastfeed during the study
• Any sign of active stage III disease as classified by the Centers for Diseases Control and Prevention
• Patients whose antiretroviral therapy contains a strong cytochrome P3A4 inhibitor (ritonavir or cobicistat) or efavirenz
• Patients receiving long-term NSAIDs or corticosteroids
• Patients taking cannabis recreationally
• Patients with a personal history of psychotic disorders
• Patients with a history of severe cerebrovascular disease (ischemic or hemorrhagic stroke)
• Renal failure defined by creatinine clearance \<60 mL / min calculated according to MDRD
• Patient with severe hepatic impairment (class C) according to the Child Pugh score
• Unstable liver disease (defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices or persistent jaundice), cirrhosis, known biliary abnormality.
• Disease or history of severe cardiovascular or cerebrovascular disorders (MI, stroke)
• Anticipated need for hepatitis C virus treatment during the randomization phase of the study.
• History or presence of allergy or intolerance to cannabidiol or to the terpenes contained in the study product.
• Active malignant tumor
• Patient who, in the opinion of the investigator, presents a significant risk of suicide

Sponsors & Collaborators

• Centre Hospitalier Régional d'Orléans: lead

Study Sites (1)

Centre Hospitalier Régional d'Orléans, France

Orléans, 45000, France

Location

Related Publications (5)

• Guittaut M, Charpentier S, Normand T, Dubois M, Raimond J, Legrand A. Identification of an internal gene to the human Galectin-3 gene with two different overlapping reading frames that do not encode Galectin-3. J Biol Chem. 2001 Jan 26;276(4):2652-7. doi: 10.1074/jbc.m002523200.

  PMID: 11160123 BACKGROUND

• Raimond J, Rouleux F, Monsigny M, Legrand A. The second intron of the human galectin-3 gene has a strong promoter activity down-regulated by p53. FEBS Lett. 1995 Apr 17;363(1-2):165-9. doi: 10.1016/0014-5793(95)00310-6.

  PMID: 7729540 BACKGROUND

• Gonzalez P, Robinet P, Charpentier S, Mollet L, Normand T, Dubois M, Legrand A. Apoptotic activity of a nuclear form of mitogaligin, a cell death protein. Biochem Biophys Res Commun. 2009 Jan 23;378(4):816-20. doi: 10.1016/j.bbrc.2008.11.133. Epub 2008 Dec 9.

  PMID: 19071086 BACKGROUND

• Duneau M, Boyer-Guittaut M, Gonzalez P, Charpentier S, Normand T, Dubois M, Raimond J, Legrand A. Galig, a novel cell death gene that encodes a mitochondrial protein promoting cytochrome c release. Exp Cell Res. 2005 Jan 15;302(2):194-205. doi: 10.1016/j.yexcr.2004.08.041.

  PMID: 15561101 BACKGROUND

• Robinet P, Mollet L, Gonzalez P, Normand T, Charpentier S, Brule F, Dubois M, Legrand A. The mitogaligin protein is addressed to the nucleus via a non-classical localization signal. Biochem Biophys Res Commun. 2010 Jan 29;392(1):53-7. doi: 10.1016/j.bbrc.2009.12.162. Epub 2010 Jan 7.

  PMID: 20056110 BACKGROUND

MeSH Terms

Conditions

HIV Seropositivity

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Thierry PRAZUCK, Dr

  CHR d'Orléans

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2022
• First Posted: April 1, 2022
• Study Start: May 16, 2022
• Primary Completion: February 8, 2023
• Study Completion: February 8, 2023
• Last Updated: April 3, 2023

Record last verified: 2023-03

Locations

FR (1)