HIV Infections
Conditions
Brief summary
This study will follow a group of healthy male participants for about 18 weeks to see the effect of taking Acitretin on their immune cells
Detailed description
Retinoids have been shown in in vitro and ex vivo models to have the ability to reverse latency reactivating the HIV reservoir and the potential for selective eradication of HIV-harbouring cells. We feel that acitretin shows significant potential as a potential adjuvant to current ART regimens, however, there is a lack of data to demonstrate that treatment with acitretin at normal are able to induce molecular and transcription changes consistent with the above activities. In order to provide a scientific basis for retinoid therapy in HIV infection, a Phase I trial of acitretin in human subjects is proposed.
Interventions
DRUGAcitretin
Acitretin will be provided to participants in the formulation Soriatane. Soriatane doses are oral tablets taken daily by the participant. Participants will then receive 35mg of oral acitretin (Soriatane) daily for 8 weeks during the intervention phase. Participants will be asked to return two months after completion of the acitretin course for clinical follow-up and additional phlebotomy for laboratory testing.
Sponsors
Ottawa Hospital Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male gender 2. Age 18 - 65 3. Able to provide informed consent 4. Willingness to participate in study treatment and follow-up 5. Willingness for serial phlebotomy and storage and future viro-immunological assays
Exclusion criteria
1. Female gender 2. Participants with a known hypersensitivity/allergy to the acitretin. 3. Participants who are actively participating in an experimental therapy study or who have received experimental therapy within the last 1 year. 4. Participants who are a poor medical risk because of other systemic diseases or active uncontrolled infections including HIV, Hepatitis B or C, and tuberculosis 5. Participants with impaired glucose tolerance including prediabetes or diabetes mellitus, dyslipidemia, or liver dysfunction 6. Previous or current history of mood disorder, psychosis, or suicidality 7. Participants currently receiving ongoing treatment with methotrexate, tetracyclines, or other retinoids
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | up to 5 months | Safety of Acitretin use in healthy volunteers will be assessed using safety labs and C-SSRS |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in α4β7 expression on peripherally circulating CD4 T cells | Serial phlebotomy measured over 5 months | Absolute change in α4β7 expression on peripherally circulating CD4 T cells measured using flow cytometry |
| Maximum Plasma Concentration [Cmax] | Trough concentrations measured serially over 2 months of active treatment | Serum concentrations measured by HPLC |
| Change in RIG-1 expression, p300 expression, mTOR expression | Serial phlebotomy measured over 5 months | Absolute change in RIG-1 expression by qRTPCR, and change in p300 expression by western blot, change in mTOR expression by qRTPCR and mTOR total/phosphorylated by western blot |
| Area Under the Curve [AUC]). | Trough concentrations measured serially over 2 months of active treatment | Serum concentrations measured by HPLC |
Outcome results
None listed