Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

Inducing Immune Quiescence the Genital Tract With ASA (IIQ-2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03629327
Recruitment Status : Not yet recruiting
First Posted : August 14, 2018
Last Update Posted : September 24, 2019
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Dr. Keith Fowke, University of Manitoba

Brief Summary:

There are 33.4 million individuals living with HIV/AIDS worldwide. Despite successful HIV prevention strategies such as condom use and reduction of sexual partners, HIV continues to spread at an alarming rate. In 2010, 2.6 millions of new infections were detected. In Sub-Saharan Africa, women represent the two-third of all new infections1. Despite the efforts of the scientific community, there is still no commercial vaccine or microbicide available.

To explain this natural protection against HIV, different mechanisms have been identified. These women have a unique immune phenotype that we called Immune Quiescence. This phenotype is characterized by lower expression of genes involved in cellular activation, lower resting levels of inflammatory cytokine production, lower level of systemic activated T cells, increased levels of systemic T regulatory, increased production of anti-viral anti-protease serpins at the female genital tract and reduced numbers of HIV target cells (mainly CD4+ CCR5+ T cells) in the FGT This project aims to induce an Immune Quiescence phenotype (decreasing immune activation) to prevent HIV infection


Condition or disease Intervention/treatment Phase
Hiv Drug: ASA 100mg Drug: Placebo Drug: ASA 300mg Not Applicable

Detailed Description:

HIV is an important global health issue. Globally, HIV is mostly transmitted through heterosexual sexual activity, and women bear the brunt of the pandemic as two-third are in women. New preventive strategies need to be developed to empower women to protect themselves. In Nairobi, Kenya, there are around 27 000 sex workers and despite prevention efforts, HIV incidence is very high in this vulnerable group which serves as catalyzers for HIV transmission to the community. Among those sex workers, despite being at higher risk of infection, some rare individuals remain HIV exposed seronegative (HESN). Over the years, our group has tried to understand this natural protection to HIV infection. The investigators discovered that in HESN individuals, the basal level of activation of the immune system is lower than in other people. This includes having few HIV target cells, mainly CD4+ CCR5+ T cells, in their genital tract. The investigators called this special phenotype Immune Quiescence (IQ). In a recent pilot study (Limiting HIV target cells by Inducing Immune Quiescence in the female genital tract ) the investigators showed that in non-sex worker women it is possible to decrease the proportion of HIV target cells and/or HIV co-receptor at the female genital tract by using anti-inflammatory drugs.

Herein, the investigators are proposing to conduct a follow-up study in female sex workers to determine the best drug formulation and drug size effect on reducing HIV target cell number at the female genital tract (FGT). Participants will receive acetylsalicylic acid (ASA) (100mg/day), ASA (300mg), or nothing for five months. At visit 1, the baseline immune activation level of the participants will be determined. In this way, every woman will serve as her own control thereby reducing the variation between tested and control groups. Participants will be randomized and ask to take the drug daily. Participants will be followed on a monthly basis. At each study visit, blood, cervico-vaginal lavage and cervical cells will be taken to determine the level of immune activation. This study is a critical "second step" in the rational development of HIV preventive biomedical method.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Three arms will be followed simultaneously
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Preventing HIV Infection by Targeting the Immune System Instead of the Virus
Estimated Study Start Date : January 1, 2020
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Active Comparator: ASA 300mg
Daily uptake of 300mg ASA
Drug: ASA 300mg
Participants will be randomized to take either 100mg, 300mg or placebo orally on a daily basis for a duration of 6 months
Other Name: Acetylsalicylic acid 300mg

Placebo Comparator: placebo
daily uptake of a placebo
Drug: Placebo
Participants will be randomized to take either 100mg, 300mg or placebo orally on a daily basis for a duration of 6 months
Other Name: no other name

Active Comparator: ASA 100mg
daily uptake of 100mg ASA
Drug: ASA 100mg
Participants will be randomized to take either 100mg, 300mg or placebo orally on a daily basis for a duration of 6 months
Other Name: Acetylsalicylic acid 100mg




Primary Outcome Measures :
  1. Changes in the proportion of HIV Target cells (CD4+CCR5+) [ Time Frame: Baseline and at each month; For six months following enrolment ]
    Fresh cervical mononuclear cell populations from the cytobrush/scraper will be stained with monoclonal antibodies, and analyzed by flow cytometry. Proportion of CD4+CCR5+ T cells will be assessed at baseline and over the course of the study.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Be a female. Having a female genital tract with a uterus
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age greater of 18 years and less than 45
  • Be active in sex work for five years or less
  • Uterus and cervix present
  • Willing to take daily the study drug (acetylsalicylic acid)
  • Willing to undergo pelvic exams
  • In general good health, no chronic infection and not taking any anti-inflammatory or immunosuppressors
  • Being HIV negative
  • Without any cardiovascular disease

Exclusion Criteria:

  • Age less than 18 or more than 45
  • Breastfeeding
  • Pregnant in the last 12 months
  • Presence of sexual transmissible disease or bacterial vaginosis at enrollment
  • Menopausal
  • Pregnancy (if a women becomes pregnant during the study she will be excluded)
  • Not being involve in sex work or being involved in sex work for more than 6 years
  • Having a chronic disease
  • Consumption of the medication listed in appendix entitled: list of other medication for health conditions
  • Being allergic to acetylsalicylic acid, other medication for pain or fever, tartrazine or any other medication
  • Having heartburn, stomach pain, stomach ulcer, anemia, hemophilia, kidney or liver disease, psoriasis, porphyria or other blood disease, G-6-PD deficiency, dermatitis (skin inflammation), alcoholism
  • Having a history of a diagnosed cardiovascular event, heart failure, peripheral arterial disease, angina, stoke, transient ischemic attack
  • Having a current or recurrent condition with a high risk of major bleeding
  • Having anemia
  • Current participation in a clinical trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03629327


Contacts
Layout table for location contacts
Contact: Keith R Fowke, PhD 204-789-3296 keith.fowke@umanitoba.ca
Contact: Julie Lajoie, PhD 204-789-3296 julie.lajoie@umanitoba.ca

Locations
Layout table for location information
Kenya
Kenyan Aids Control Project/University of Nairobi
Nairobi,, Kenya
Sponsors and Collaborators
University of Manitoba
Bayer

Layout table for additonal information
Responsible Party: Dr. Keith Fowke, Professor, University of Manitoba
ClinicalTrials.gov Identifier: NCT03629327    
Other Study ID Numbers: HS19749(B2016:042)
B2016:042 ( Other Identifier: University of Manitoba )
First Posted: August 14, 2018    Key Record Dates
Last Update Posted: September 24, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: we are not planing to share individuals data

Layout table for additional information
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Aspirin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics