Impact of Probiotics in HIV-positive Patients With Neurocognitive Disorders (PROCOG)

Study to Measure the Impact of Probiotics on Immune Activation and Neurocognitive Disorders in HIV-positive Patients With Neurocognitive Disorders

The prevalence of HIV-associated neurocognitive disorders (Human Immunodeficiency Virus) remains high during the era of effective triple therapy. The main clinical phenotypes of cognitive impairment are currently represented by asymptomatic neurocognitive neurocognitive impairment (ANI) and mild neurocognitive disorders (MND). In contrast, HIV-associated dementia has almost disappeared.

Among the hypotheses to explain the persistence of such a high prevalence is the persistent activation of the immune system despite virological success. This chronic immune activation is believed to be responsible for an inflammatory response and therefore for accelerated cell aging. Several organ complications in HIV-positive patients have been associated with high markers of immune activation.

Among the causes of chronic immune activation in virologically controlled patients, an imbalance in the intestinal flora is suspected. In fact, shortly after HIV infection, the virus causes significant apoptosis of intestinal lymphocytes, responsible for a loss of integrity of the intestinal barrier and an imbalance of flora, defined as "dysbiosis".

Loss of epithelial integrity and intestinal dysbiosis are suspected of causing systemic passage of bacterial fragments, of which lypopolisaccharide is best known, resulting in chronic activation of the immune system. Several studies suggest a link between digestive bacterial translocation and HIV-related neurocognitive disorders. An improvement in intestinal dysbiosis could therefore contribute to reducing immune activation and the severity of cognitive impairment. A recent study showed that probiotics can reduce levels of neopterin, a marker of monocytic activation, in the cerebrospinal fluid of HIV-positive patients without neurological symptoms.

Our objective is to evaluate the impact of probiotic supplementation on immune activation and cognitive performance in virologically controlled HIV-positive patients with a diagnosis of ANI or MND. The potential improvement of cognition through probiotic treatment could therefore improve their quality of life at a lower cost than a drug and without the risk of serious side effects.

Study Overview

• Status: Recruiting
• Conditions: Neurocognitive Disorders; HIV
• Intervention / Treatment: Dietary supplement: Vivomixx

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chrisine LEBRUN FRENAY, PUPH; Phone Number: 33492038754; Email: lebrun-frenay.c@chu-nice.fr

Study Locations

• France
  • Cannes, France, 06400
    • Recruiting
    • Ch Cannes
    • Contact: Matteo VASSALLO, PH; Email: M.VASSALLO@ch-cannes.fr
  • Montpellier, France, 34000
    • Not yet recruiting
    • CHU Montpellier
    • Contact: Jacques Reynes, PUPH; Email: j-reynes@chu-montpellier.fr
  • Nice, France, 06000
    • Recruiting
    • Chu de Nice
    • Contact: Christine LEBRUN FRENAY, PUPH; Phone Number: 33492038754; Email: lebrun-frenay@chu-nice.fr
    • Sub-Investigator: Jacques DURANT

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:

• Patients who have signed informed consent
• Patients infected with HIV-1
• Patients with undetectable viral load and stable antiretroviral therapy for at least 6 months
• Patients with HIV-related neurocognitive disorders of the ANI or MND type, to be confirmed by neuropsychological assessment at inclusion
• Outpatient patients, over 18 years of age
• Patients with social security coverage

Exclusion Criteria:

• Patients infected with HIV-2
• Patients who have not been on stable antiretroviral therapy and have been virologically successful for at least 6 months
• Patients who have been treated during the primary infection phase, taking into account the potential risks of impact on intestinal lymphocyte apoptosis and therefore on the microbiota
• Patients who do not have HIV-related neurocognitive disorders such as ANI or MND
• Patients refusing to participate in the study
• Patients consuming probiotics at inclusion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: probiotics; probiotic administration	Dietary supplement: Vivomixx; probiotic administration: administration of two sachets per day (one in the morning and one in the evening) during 6 months
No Intervention: without probiotic; no change from the usual care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
measurement of the immune activation and Serum inflammation markers	The immune activation is composed with the following elements (quantity of serum immune activation and inflammation markers : sCD14 (ng/mL), sCD163 (ng/mL), TNF-alpha (ng/ml) , IL-1 (ng/ml) , IL-6 (ng/ml) , IL-8 (ng/ml) , D-Dimeres (ng/ml), hCRP (ng/ml), MCP-1(ng/ml), IP-10 (ng/ml), Neurofilaments light chain (log10 ng/ml) and Lipopolysaccharide (ng/ml)) , at inclusion and after 6 months of probiotic supplementation in the 2 groups wwith laboratory tests. The immune activation is the result of the multiple measurements. there is no units of measure and it's not an aggregation of the measurement.	6 months

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nice

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2019
• Primary Completion (Anticipated): December 15, 2021
• Study Completion (Anticipated): April 15, 2022

Study Registration Dates

• First Submitted: September 6, 2019
• First Submitted That Met QC Criteria: November 21, 2019
• First Posted (Actual): November 22, 2019

Study Record Updates

• Last Update Posted (Actual): July 22, 2021
• Last Update Submitted That Met QC Criteria: July 21, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Disease; Neurocognitive Disorders
• Other Study ID Numbers: 19-AOI-03

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No