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Effect of Isotretinoin on Immune Activation Among HIV-1 Infected Subjects With Incomplete CD4+ T Cell Recovery

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01969058
First Posted: October 25, 2013
Last Update Posted: December 13, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
AIDS Clinical Trials Group
Results First Submitted: August 4, 2017  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: HIV-1 Infection
Intervention: Drug: Isotretinoin

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
First participant was enrolled on July 2, 2014. Accrual to the study closed on May 5, 2016, with 15 U.S and Puerto Rico sites registered and enrolled participants

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were randomized 2:1 to Isotretinoin and no study treatment arms. Randomization was stratified by willingness to participate in the gut biopsy substudy, A5330s.

Reporting Groups
  Description
Isotretinoin Arm Participants received Isotretinoin at approximately 0.5 mg/kg orally once daily for 4 weeks, then increased to approximately 1.0 mg/kg orally once daily for 12 weeks.
No Study Treatment Arm No Isotretinoin treatment

Participant Flow:   Overall Study
    Isotretinoin Arm   No Study Treatment Arm
STARTED   50   26 
COMPLETED   47   26 
NOT COMPLETED   3   0 
Withdrawal by Subject                2                0 
Adverse Event                1                0 



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All enrolled participants

Reporting Groups
  Description
Isotretinoin Arm Participants received Isotretinoin at approximately 0.5 mg/kg orally once daily for 4 weeks, then increased to approximately 1.0 mg/kg orally once daily for 12 weeks.
No Study Treatment Arm No Isotretinoin treatment
Total Total of all reporting groups

Baseline Measures
   Isotretinoin Arm   No Study Treatment Arm   Total 
Overall Participants Analyzed 
[Units: Participants]
 50   26   76 
Age 
[Units: Years]
Median (Inter-Quartile Range)
     
Participants Analyzed 
[Units: Participants]
 50   26   76 
   49 
 (38 to 55) 
 51 
 (38 to 53) 
 49 
 (38 to 55) 
Age, Customized 
[Units: Participants]
Count of Participants
     
18-39 years       
Participants Analyzed 
[Units: Participants]
 50   26   76 
18-39 years   14   7   21 
40-59 years       
Participants Analyzed 
[Units: Participants]
 50   26   76 
40-59 years   31   16   47 
>=60 years       
Participants Analyzed 
[Units: Participants]
 50   26   76 
>=60 years   5   3   8 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Participants Analyzed 
[Units: Participants]
 50   26   76 
Female      4   8.0%      1   3.8%      5   6.6% 
Male      46  92.0%      25  96.2%      71  93.4% 
Race/Ethnicity, Customized 
[Units: Participants]
Count of Participants
     
Non-Hispanic White       
Participants Analyzed 
[Units: Participants]
 50   26   76 
Non-Hispanic White   18   12   30 
Non-Hispanic Black       
Participants Analyzed 
[Units: Participants]
 50   26   76 
Non-Hispanic Black   21   9   30 
Hispanic (Regardless of Race)       
Participants Analyzed 
[Units: Participants]
 50   26   76 
Hispanic (Regardless of Race)   11   5   16 
Region of Enrollment 
[Units: Participants]
Count of Participants
     
Puerto Rico       
Participants Analyzed 
[Units: Participants]
 50   26   76 
Puerto Rico   1   0   1 
United States       
Participants Analyzed 
[Units: Participants]
 50   26   76 
United States   49   26   75 
HIV-1 RNA 
[Units: Participants]
Count of Participants
     
>= Assay lower limit (40 copies/mL)       
Participants Analyzed 
[Units: Participants]
 50   26   76 
>= Assay lower limit (40 copies/mL)   0   1   1 
< Assay lower limit (40 copies/mL)       
Participants Analyzed 
[Units: Participants]
 50   26   76 
< Assay lower limit (40 copies/mL)   50   25   75 
CD4+ Cell Count 
[Units: Cells/mm^3]
Median (Inter-Quartile Range)
     
Participants Analyzed 
[Units: Participants]
 50   26   76 
   549 
 (299 to 754) 
 556 
 (342 to 781) 
 552 
 (310 to 768) 
BMI 
[Units: Kg/m^2]
Median (Inter-Quartile Range)
     
Participants Analyzed 
[Units: Participants]
 50   26   76 
   27.1 
 (23.1 to 29.3) 
 26.9 
 (22.6 to 27.9) 
 27.1 
 (22.9 to 29.2) 
CD8+ T-cell Activation Percent [1] [2] 
[Units: Percentage of cells]
Median (Inter-Quartile Range)
     
Participants Analyzed 
[Units: Participants]
 39   26   65 
   13.67 
 (10.35 to 19.49) 
 13.40 
 (8.43 to 18.56) 
 13.66 
 (9.83 to 19.29) 
[1]

CD8+ T-cell activation percent is the primary endpoint. Level of CD8+ T-cell activation was determined by measuring the percentage of cells that expressed both the activation marker CD38+ and Human leukocyte antigen (HLA)-DR+.

Baseline is defined as the average of pre-entry and entry values

[2] The primary endpoint is limited to participants who have data for both baseline and week 14/16, (for the Isotretinoin arm) completed treatment (allowing ≤8 missed doses), did not use prohibited medications, and did not experience virologic failure from baseline to week 16.


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change in CD8+ T-cell Activation From Baseline to Week 14/16   [ Time Frame: baseline, week 14/16 ]

2.  Secondary:   Change in CD8+ T-cell Activation   [ Time Frame: baseline, week 14/16, week 28 ]

3.  Secondary:   Change in sCD14   [ Time Frame: baseline, week 14/16, week 28 ]

4.  Secondary:   Change in I-FABP   [ Time Frame: baseline, week 14/16, week 28 ]

5.  Secondary:   Change in IL-6   [ Time Frame: baseline, week 14/16, week 28 ]

6.  Secondary:   Change in hsCRP   [ Time Frame: baseline, week 14/16, week 28 ]

7.  Secondary:   Change in sTNF-r1   [ Time Frame: baseline, week 14/16, week 28 ]

8.  Secondary:   Change in sTNF-r2   [ Time Frame: baseline, week 14/16, week 28 ]

9.  Secondary:   Change in D-dimer   [ Time Frame: baseline, week 14/16, week 28 ]

10.  Secondary:   Change in TF   [ Time Frame: baseline, week 14/16, week 28 ]

11.  Secondary:   Change in sCD163   [ Time Frame: baseline, week 14/16, week 28 ]

12.  Secondary:   Change in CD4+ T-cell Count   [ Time Frame: baseline, week 14/16, week 28 ]

13.  Secondary:   Change in Cell-associated HIV-1 RNA   [ Time Frame: baseline, week 14/16, week 28 ]

14.  Secondary:   Cell-associated HIV-1 DNA   [ Time Frame: baseline, week 14/16, week 28 ]

15.  Secondary:   Primary Targeted Adverse Events   [ Time Frame: from study entry to end of study (week 28) ]

16.  Secondary:   Change in Treg Frequency   [ Time Frame: baseline, week 14/16, week 28 ]
Results not yet reported.   Anticipated Reporting Date:   06/2018  

17.  Secondary:   Change in Th17 Frequency   [ Time Frame: baseline, week 14/16, week 28 ]
Results not yet reported.   Anticipated Reporting Date:   06/2018  

18.  Secondary:   Change in Endogenous Retinoid Metabolite Profiles   [ Time Frame: baseline, week 14/16, week 28 ]
Results not yet reported.   Anticipated Reporting Date:   06/2018  

19.  Secondary:   Pharmacokinetics – Trough Concentrations of Isotretinoin and Antiviral Treatment (ART)   [ Time Frame: study entry, weeks 8, 12, 16, 20 and 24 ]
Results not yet reported.   Anticipated Reporting Date:   06/2018  


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: ACTG Clinicaltrials.gov Coordinator
Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.
phone: (301) 628-3313
e-mail: ACTGCT.Gov@s-3.com



Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT01969058     History of Changes
Other Study ID Numbers: ACTG A5325
UM1AI068636 ( U.S. NIH Grant/Contract )
First Submitted: August 21, 2013
First Posted: October 25, 2013
Results First Submitted: August 4, 2017
Results First Posted: September 5, 2017
Last Update Posted: December 13, 2017