RA Effect on Cell Surface Molecules in Vivo

Study Overview
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Brief Summary
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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
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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.

Official Title
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Retinoic Acid Effect on Cell Surface Molecules in Vivo

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Acitretin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male gender Age 18 - 65 Able to provide informed consent Willingness to participate in study treatment and follow-up Willingness for serial phlebotomy and storage and future viro-immunological assays Exclusion Criteria: Female gender Participants with a known hypersensitivity/allergy to the acitretin. Participants who are actively participating in an experimental therapy study or who have received experimental therapy within the last 1 year. Participants who are a poor medical risk because of other systemic diseases or active uncontrolled infections including HIV, Hepatitis B or C, and tuberculosis Participants with impaired glucose tolerance including prediabetes or diabetes mellitus, dyslipidemia, or liver dysfunction Previous or current history of mood disorder, psychosis, or suicidality Participants currently receiving ongoing treatment with methotrexate, tetracyclines, or other retinoids

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acitretin treatment<br> | Drug: Acitretin<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | Safety of Acitretin use in healthy volunteers will be assessed using safety labs and C-SSRS | up to 5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in α4β7 expression on peripherally circulating CD4 T cells | Absolute change in α4β7 expression on peripherally circulating CD4 T cells measured using flow cytometry | Serial phlebotomy measured over 5 months | 
| Maximum Plasma Concentration [Cmax] | Serum concentrations measured by HPLC | Trough concentrations measured serially over 2 months of active treatment | 
| Change in RIG-1 expression, p300 expression, mTOR expression | 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 | Serial phlebotomy measured over 5 months | 
| Area Under the Curve [AUC]). | Serum concentrations measured by HPLC | Trough concentrations measured serially over 2 months of active treatment |