HIVIIQNCT02079077
Inducing Immune Quiescence to Prevent HIV Infection in Women
A study testing Acetylsalicylic Acid (ASA) and Hydroxychloroquine (HCQ) in people with HIV, run by University of Manitoba at 1 site in Kenya.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 50 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- HIV
- What is being tested?
- Acetylsalicylic Acid (ASA) and Hydroxychloroquine (HCQ)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 91 participants
- Where
- 1 siteKenya
- Study dates
- Apr 2014to 1 Jan 2018
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age greater than 18 years old and less than 50 years old
- Uterus and cervix present
- Willing to take daily acetylsalicylic acid or HCQ
- 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
- Being active in sex work (for the Female commercial sex worker group)
Who cannot join
- Age less than 18 years or more than 50 years old
- Pregnancy (if a women becomes pregnant during the 10 weeks of the project she will be excluded)
- Breast feeding
- Pregnant in the last 12 months
- Being positive for Sexual transmissible disease or bacterial vaginosis at week 0
- Menopausal
Show all 18Show fewer
- No longer involve in sex work (for the female sex worker group)
- Having a chronic disease
- Taking any of the medication listed in annex 1 for health conditions
- Being allergic to acetylsalicylic acid, other medication for pain or fever, tartrazine dye or chloroquine, hydroxuchloroquine, primaquine 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 experienced previous vision changes while taking chloroquine, hydroxychloroquine (Aralen) or primaquine.
- 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
- -
- -
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Limiting HIV Target Cells by Inducing Immune Quiescence in the Female Genital Tract
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.
Read the 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:
- 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.
- 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.
- 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
- 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.) .
- Conditions
- HIV
- Being tested
- Acetylsalicylic Acid (ASA), Hydroxychloroquine (HCQ)
- Keywords
- HIV, Immune quiescence, ASA, Hydroxychloroquin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acetylsalicylic Acid (ASA)Drug
Acetylsalicylic Acid (ASA) 81 mg. oral daily for two months
Hydroxychloroquine (HCQ)Drug
Hydroxychloroquine (HCQ) 200 mg. oral, daily for two months.
| Study group | Role | What they receive |
|---|---|---|
| Acetylsalicylic Acid (ASA) | Other | ASA 81 mg. p.o. daily for two months Receives: Drug: Acetylsalicylic Acid (ASA) |
| Hydroxychloroquine (HCQ) | Other | Hydroxychloroquine (HCQ) 200 mg. o.d. p.o. for two months. Receives: Drug: Hydroxychloroquine (HCQ) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Systemic Immune Activation From Baseline Observed by the CD69 Expression on CD4 T Cells
We will analyse reduce of immune activation by measuring change in T cell activation (CD69) between baseline and every month during drug administration phase (8 weeks).
Measured: Baseline and 8 weeks
Secondary outcomes (1)
Change in Number of CCR5+CD4+ T Cell Population at the Female Genital Tract.
We will measure changes in the number of CD4+T cells expressing CCR5 at the female genital tract before and at the end of the study.
Measured: baseline and 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2014 (estimated)
- Study startApr 2014
- Primary completionDec 2015
- Study completion1 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by University of ManitobaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 91 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Manitoba
- Sponsor type
- University, hospital or other
- Collaborators
- University of Nairobi
- Responsible party
- Principal investigator, Dr. Keith Fowke, University of Manitoba
- Investigators
- Keith R. Fowke, PhD, Principal investigator, University of Manitoba
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02079077
- Sponsor's protocol ID
- B2013:042
- Other IDs
- MOP#86721, S5-0386-01
- Acronym
- IIQ
- Status last verified
- Sep 2019
- First submitted
- 3 Mar 2014
- Last updated
- 10 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Lajoie J, Kowatsch MM, Mwangi LW, Boily-Larouche G, Oyugi J, Chen Y, Kimani M, Ho EA, Kimani J, Fowke KR. Low-Dose Acetylsalicylic Acid Reduces T Cell Immune Activation: Potential Implications for HIV Prevention. Front Immunol. 2021 Nov 18;12:778455. doi: 10.3389/fimmu.2021.778455. eCollection 2021.
PubMed 34868050Lajoie J, Mwangi L, Fowke KR. Preventing HIV infection without targeting the virus: how reducing HIV target cells at the genital tract is a new approach to HIV prevention. AIDS Res Ther. 2017 Sep 12;14(1):46. doi: 10.1186/s12981-017-0166-7.
PubMed 28893304
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Limiting HIV Target Cells by Inducing Immune Quiescence in the Female Genital Tract
- ClinicalTrials.gov ID
- NCT02079077
- Acronym / sponsor ID
- IIQ / B2013:042
- Conditions
- HIV
- Keywords
- HIV, Immune quiescence, ASA, Hydroxychloroquin
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 91 participants (actual)
- Lead sponsor
- University of ManitobaUniversity, hospital or other
- Collaborators
- University of Nairobi
- Study start
- Apr 2014
- Primary completion
- Dec 2015 (actual)
- Study completion
- 1 Jan 2018 (actual)
- First posted
- 5 Mar 2014 (estimated)
- Results
- Posted 10 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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:
- 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.
- 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.
- 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
- 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.) .
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Acetylsalicylic Acid (ASA) | Other | Drug: Acetylsalicylic Acid (ASA)ASA 81 mg. p.o. daily for two months |
| Hydroxychloroquine (HCQ) | Other | Drug: Hydroxychloroquine (HCQ)Hydroxychloroquine (HCQ) 200 mg. o.d. p.o. for two months. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Age greater than 18 years old and less than 50 years old
- Uterus and cervix present
- Willing to take daily acetylsalicylic acid or HCQ
- Willing to undergo pelvic exams
- In general good health, no chronic infection and not taking any anti-inflammatory or immunosuppressors
Key exclusion criteria (18 listed)
- Age less than 18 years or more than 50 years old
- Pregnancy (if a women becomes pregnant during the 10 weeks of the project she will be excluded)
- Breast feeding
- Pregnant in the last 12 months
- Being positive for Sexual transmissible disease or bacterial vaginosis at week 0
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Acetylsalicylic Acid (ASA)Acetylsalicylic Acid (ASA) 81 mg. oral daily for two months | Drug | Acetylsalicylic Acid (ASA) |
| Hydroxychloroquine (HCQ)Hydroxychloroquine (HCQ) 200 mg. oral, daily for two months. | Drug | Hydroxychloroquine (HCQ) |
Primary outcome
Changes in Systemic Immune Activation From Baseline Observed by the CD69 Expression on CD4 T Cells
Time frame: Baseline and 8 weeks
We will analyse reduce of immune activation by measuring change in T cell activation (CD69) between baseline and every month during drug administration phase (8 weeks).
1 secondary outcome
Change in Number of CCR5+CD4+ T Cell Population at the Female Genital Tract.
Time frame: baseline and 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34868050Lajoie J, Kowatsch MM, Mwangi LW, Boily-Larouche G, Oyugi J, Chen Y, Kimani M, Ho EA, Kimani J, Fowke KR. Low-Dose Acetylsalicylic Acid Reduces T Cell Immune Activation: Potential Implications for HIV Prevention. Front Immunol. 2021 Nov 18;12:778455. doi: 10.3389/fimmu.2021.778455. eCollection 2021.
- Derived from this study: PubMed 28893304Lajoie J, Mwangi L, Fowke KR. Preventing HIV infection without targeting the virus: how reducing HIV target cells at the genital tract is a new approach to HIV prevention. AIDS Res Ther. 2017 Sep 12;14(1):46. doi: 10.1186/s12981-017-0166-7.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Keith R. Fowke, PhD principal investigator
University of Manitoba
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Acetylsalicylic Acid (ASA) and Hydroxychloroquine (HCQ) in people with HIV, run by University of Manitoba at 1 site in Kenya.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Kenya. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in Systemic Immune Activation From Baseline Observed by the CD69 Expression on CD4 T Cells (time frame: Baseline and 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02079077, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2019.