RA Effect on Cell Surface Molecules in Vivo

Phase 1

Withdrawn

• Conditions: HIV Infections
• Interventions: Drug: Acitretin

• Registration Number: NCT03753867
• Lead Sponsor: Ottawa Hospital Research Institute

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.

Study Timeline

• Study First Submitted: 2018-10-01
• Study First Submitted QC: 2018-11-23
• Study First Posted: 2018-11-27
• Study Start: 2019-01-07
• Primary Completion: 2019-05-08
• Study Completion: 2019-05-08
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-02
• Last Update Posted: 2020-03-04

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: Male
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Acitretin treatment	Acitretin	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
Area Under the Curve [AUC]).	Trough concentrations measured serially over 2 months of active treatment	Serum concentrations measured by HPLC
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