Inducing Immune Quiescence to Prevent HIV Infection in Women (IIQ)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University of Manitoba
Sponsor:
Collaborator:
University of Nairobi
Information provided by (Responsible Party):
Dr. Keith Fowke, University of Manitoba
ClinicalTrials.gov Identifier:
NCT02079077
First received: March 3, 2014
Last updated: July 16, 2014
Last verified: July 2014
  Purpose

In this project, the investigators want to analyse the capacity of Acetylsalicylic acid and hydoxychlroquin (HCQ) to induce an Immune Quiescence (IQ) phenotype, which has been previously associated with natural protection to HIV infection. 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 ( female genital tract).

The objective of this study is to determine if daily oral administration of Acetylsalicylic acid or hydroxychlroroquin can reduce systemic and mucosal immune activation in HIV negative women.


Condition Intervention
HIV
Drug: Acetylsalicylic Acid (ASA)
Drug: Hydroxychloroquine (HCQ)

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Limiting HIV Target Cells by Inducing Immune Quiescence in the Female Genital Tract

Resource links provided by NLM:


Further study details as provided by University of Manitoba:

Primary Outcome Measures:
  • Change in systemic immune activation from baseline observed by a decrease of HLA-DR and CD69 expression on CD4 T cells [ Time Frame: Baseline and 8 weeks ] [ Designated as safety issue: No ]
    We will analyse reduce of immune activation by measuring change in T cell activation (HLA-DR and CD69) and the systemic pro-inflammatory immune environment (cytokine and chemokine) between baseline and every month during drug administration phase (8 weeks).


Secondary Outcome Measures:
  • Change in number of HIV target cells from baseline by reduction of CCR5+CD4+ T cell population at the female genital tract. [ Time Frame: baseline and 8 weeks ] [ Designated as safety issue: No ]
    We will measure CCR5 expression on CD4+T cells the female genital tract before and at the end of the study.


Estimated Enrollment: 160
Study Start Date: April 2014
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Acetylsalicylic Acid (ASA)
ASA 81 mg. p.o. daily for two months
Drug: Acetylsalicylic Acid (ASA)
Acetylsalicylic Acid (ASA) 81 mg. oral daily for two months
Other Name: Acetylsalicylic Acid (ASA)
Hydroxychloroquine (HCQ)
Hydroxychloroquine (HCQ) 200 mg. o.d. p.o. for two months.
Drug: Hydroxychloroquine (HCQ)
Hydroxychloroquine (HCQ) 200 mg. oral, daily for two months.
Other Name: Hydroxychloroquine (HCQ)

Detailed Description:

The investigators will enrol 80 non female sex work low-risk HIV negative women and 80 HIV negative female sex worker HIV negative form Nairobi, Kenya and followed for a 3 months period.

During the first month, samples will be taken on a monthly basis

  • blood,
  • vaginal samples: cytobrush/scarper and cervico vaginal lavage (CVL). This is done to determine the baseline levels of systemic and mucosal immune activation of each woman. In this way, every women is acting as her own control thereby reducing variation between control and participant.

Chemokine/cytokine level, as well as cellular immune activation and T regulatory cells will be assessed.

At month two: the women will be divided in two different arms (oral administration of hydroxychloroquine: 200mg/day or Acetylsalicylic acid 81mg/day) and followed, on a monthly basis, for an 8 additional weeks.

During this time, monthly blood and vaginal samples (cytobrush/scraper and CVL) the investigators will be taken. They will measure change in the systemic and mucosal immune activation.

Immune Quiescence phenotype (decrease of T cells immune activation, lower immune genes activation expression and pro-inflammatory cytokine/chemokine expression) will be evaluated by flow cytometry, microarray, and multiplex bead array technology.

Here is how samples will be taken:

  1. A sample of cervical mucus will be collected by using a cotton swab rotated 360º in the cervical os, and a second swab used to collect secretions from the posterior vaginal fornix. Both swabs will be transferred into a single vial containing 5 mL of phosphate-buffered saline (PBS) which will be transported to the laboratory to be tested and cultured for sexually transmitted infections such as gonorrhea, chlamydia etc.
  2. Cervical cells will be collected by using a small brush and a wooden spatula. Both specimen will be transferred into a 15ml conical tube containing 5 ml of PBS. This specimen will be used to characterize the cellular populations in the specimen.
  3. Cervico vaginal lavage will be performed by washing the endocervix with 2 ml of sterile 1x PBS. The liquid will be collected form the posterior fornix. Samples will be placed into a conical tube, centrifuged to remove cellular debris and the supernatant will be stored at -70°C and will be shipped in liquid nitrogen dry shipper to Winnipeg, Manitoba. Those specimens will be used for innate soluble factor detection (chemokines, cytokines, antibodies, innate protein, etc
  4. 30ml of venous blood will be taken. (Peripheral Blood Mononuclear Cells will be extracted for immune activation analysis, DNA will be used for immune genes expression, plasma will be used for protein and innate soluble factor detection.)

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  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria:

  1. Age greater than 18 years old and less than 50 years old
  2. Uterus and cervix present
  3. Willing to take daily acetylsalicylic acid or HCQ
  4. Willing to undergo pelvic exams
  5. In general good health, no chronic infection and not taking any anti-inflammatory or immunosuppressors
  6. Being HIV negative
  7. Without any cardiovascular disease
  8. Being active in sex work (for the Female commercial sex worker group)

Exclusion criteria:

  1. Age less than 18 years or more than 50 years old
  2. Pregnancy (if a women becomes pregnant during the 10 weeks of the project she will be excluded)
  3. Breast feeding
  4. Pregnant in the last 12 months
  5. Being positive for Sexual transmissible disease or bacterial vaginosis at week 0
  6. Menopausal
  7. No longer involve in sex work (for the female sex worker group)
  8. Having a chronic disease
  9. Taking any of the medication listed in annex 1 for health conditions
  10. Being allergic to acetylsalicylic acid, other medication for pain or fever, tartrazine dye or chloroquine, hydroxuchloroquine, primaquine or any other medication
  11. 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
  12. Having experienced previous vision changes while taking chloroquine, hydroxychloroquine (Aralen) or primaquine.
  13. Having a history of a diagnosed cardiovascular event, heart failure, peripheral arterial disease, angina, stoke, transient ischemic attack
  14. Having a current or recurrent condition with a high risk of major bleeding
  15. Having anemia
  16. Current participation in a clinical trial

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  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02079077

Contacts
Contact: Julie Lajoie, PhD 204-789-3296 julie.lajoie1@gmail.com
Contact: Joshua Kimani, Dr. jkimani@csrtkenya.org

Locations
Kenya
Kenyan Aids Control Project/University of Nairobi Recruiting
Nairobi,, Kenya
Contact: Joshua Kimani, Dr.       jkimani@csrtkenya.org   
Sponsors and Collaborators
University of Manitoba
University of Nairobi
Investigators
Principal Investigator: Keith R. Fowke, PhD University of Manitoba
  More Information

No publications provided

Responsible Party: Dr. Keith Fowke, Professor Department of Medical Microbiology, University of Manitoba
ClinicalTrials.gov Identifier: NCT02079077     History of Changes
Other Study ID Numbers: B2013:042, MOP#86721, S5-0386-01
Study First Received: March 3, 2014
Last Updated: July 16, 2014
Health Authority: Canada: Canadian Institutes of Health Research

Keywords provided by University of Manitoba:
HIV, Immune quiescence, ASA, Hydroxychloroquin

Additional relevant MeSH terms:
Aspirin
Hydroxychloroquine
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Central Nervous System Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on September 18, 2014