RA Effect on Cell Surface Molecules in Vivo

HIV Infections Clinical Trial

Official title:

Retinoic Acid Effect on Cell Surface Molecules in Vivo

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03753867
• Other study ID #: 2018 0639
• Status: Withdrawn
• Phase: Phase 1
• Start date: January 7, 2019
• Est. completion date: May 8, 2019

Study information

• Verified date: March 2020
• Source: Ottawa Hospital Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: May 8, 2019
• Est. primary completion date: May 8, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Acitretin
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Ottawa Hospital Research Institute

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change in a4ß7 expression on peripherally circulating CD4 T cells	Absolute change in a4ß7 expression on peripherally circulating CD4 T cells measured using flow cytometry	Serial phlebotomy measured over 5 months
Secondary	Maximum Plasma Concentration [Cmax]	Serum concentrations measured by HPLC	Trough concentrations measured serially over 2 months of active treatment
Secondary	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
Secondary	Area Under the Curve [AUC]).	Serum concentrations measured by HPLC	Trough concentrations measured serially over 2 months of active treatment