NCT01969058

Brief Summary

This phase II study was done in HIV-infected participants on antiretroviral therapy to evaluate the effects of isotretinoin (a drug that is approved for use in the treatment of severe acne) on the immune system. The immune system helps the body fight infections. When the immune system is not working well, one may be at greater risk for diseases that are common in aging, like heart disease, weaker bones, and kidney disease.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
76

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Jul 2014

Geographic Reach
2 countries

15 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 21, 2013

Completed
2 months until next milestone

First Posted

Study publicly available on registry

October 25, 2013

Completed
8 months until next milestone

Study Start

First participant enrolled

July 2, 2014

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 31, 2016

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2016

Completed
10 months until next milestone

Results Posted

Study results publicly available

September 5, 2017

Completed
Last Updated

October 15, 2024

Status Verified

October 1, 2024

Enrollment Period

2.2 years

First QC Date

August 21, 2013

Results QC Date

August 4, 2017

Last Update Submit

October 1, 2024

Conditions

HIV-1 Infection

Keywords

IsotretinoinHIV-1immunology markersimmune activationviral suppression

Outcome Measures

Primary Outcomes (1)

  • Change in CD8+ T-cell Activation From Baseline to Week 14/16

    Level of CD8+ T-cell activation was determined by measuring the percentage of CD8+ T-cells that expressed both the activation marker CD38+ and Human leukocyte antigen (HLA)-DR+. The endpoint is measuring the change from baseline to week 14/16, where baseline is defined as the average of pre-entry and entry, and week 14/16 is defined as the average of week 14 and week 16. Change = (week 14/16 - baseline).

    baseline, week 14/16

Secondary Outcomes (20)

  • Change in CD8+ T-cell Activation

    baseline, week 14/16, week 28

  • Change in sCD14

    baseline, week 14/16, week 28

  • Change in I-FABP

    baseline, week 14/16, week 28

  • Change in IL-6

    baseline, week 14/16, week 28

  • Change in hsCRP

    baseline, week 14/16, week 28

  • +15 more secondary outcomes

Study Arms (2)

Isotretinoin Arm

ACTIVE COMPARATOR

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.

Drug: Isotretinoin

No study treatment Arm

NO INTERVENTION

No Isotretinoin treatment

Interventions

IsotretinoinDRUG

Isotretinoin is a drug that is approved for use in the treatment of severe acne. The aim of this study is to evaluate the role of Isotretinoin on immune activation and inflammation.

Also known as: 13-cis-retinoic acid
Isotretinoin Arm

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • \- HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load.
  • NOTE: The term "licensed" refers to a US FDA-approved kit, which is required for all IND studies.
  • CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (eg, indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load.
  • Receiving ART therapy for at least 12 months prior to study entry.
  • No plans to change the ART regimen in the 6 months after study entry.
  • HIV-1 RNA below the lower limit of detection using an FDA-approved assay obtained within 30 days prior to study entry by any laboratory that has a CLIA certification or its equivalent (eg, \<50 copies/mL on Roche Amplicor HIV-1 Monitor assay, \<75 copies/mL on the Versant HIV-1 RNA assay by branched DNA, \<40 copies/mL on the Abbott m2000sp/m2000rt real-time PCR test, \< 20 copies/mL on the COBAS AmpliPrep/TAQMAN HIV-1 assay).
  • All measurements of HIV-1 RNA within the 12 months prior to study entry must be below the limit of detection with the following exception:
  • NOTE A: 1 viral blip (\<200 copies/mL) is permitted if it is preceded and followed by viral loads below the limits of detection.
  • NOTE B: The virologic assay must have a lower limit of detection of ≤ 75 copies/mL.
  • CD4+ cell count \<350 cells/mm3 obtained at screening within 30 days prior to entry at any laboratory that has a CLIA (Clinical Laboratory Improvement Amendments) certification or its equivalent.
  • The following laboratory values obtained within 30 days prior to entry by any laboratory that has a CLIA certification or its equivalent:
  • Hemoglobin A1c (HgbA1c) levels ≤ 6.5%
  • Hemoglobin ≥ 9.0 g/dL
  • Platelet count ≥ 50,000/mm3
  • Creatinine ≤1.5 mg/dl
  • +19 more criteria

You may not qualify if:

  • Pre-existing diagnosis of diabetes.
  • Currently receiving treatment with fibrate, nicotinic acid, tetracycline, fish oil \>1g/d, or methotrexate.
  • Known active healing fracture or any severe bone disorders. NOTE: does not include healed fractures or history of old fractures.
  • Receipt of any of the following medications within 30 days prior to entry: systemic steroids (including intra-articular steroids; inhaled or nasal steroid therapy is permitted), interleukins, systemic interferons (including intra-articular steroid injection; local injection of interferon alpha for treatment of human papilloma virus is permitted), or systemic chemotherapy.
  • Known allergy/sensitivity or any hypersensitivity to vitamin A, retinoids, or any of their derivatives.
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
  • Acute or serious illness requiring systemic treatment and/or hospitalization within 60 days prior to entry.
  • Weight \< 40 kg or \> 150 kg.
  • History of major depression or suicide attempt requiring hospitalization, or psychotic episode requiring medication or hospitalization.
  • History of inflammatory bowel disease such as Crohn's disease, or Ulcerative colitis.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (15)

31788 Alabama CRS

Birmingham, Alabama, 35294, United States

Location

601 University of California, Los Angeles CARE Center CRS

Los Angeles, California, 90035, United States

Location

801 University of California, San Francisco HIV/AIDS CRS

San Francisco, California, 94110, United States

Location

101 Massachusetts General Hospital (MGH) CRS

Boston, Massachusetts, 02114, United States

Location

107 Brigham and Women's Hosp. ACTG CRS

Boston, Massachusetts, 02115, United States

Location

2101 Washington University Therapeutics (WT) CRS

St Louis, Missouri, 63110, United States

Location

31786 New Jersey Medical School Clinical Research Center CRS

Newark, New Jersey, 07103, United States

Location

31787 University of Rochester Adult HIV Therapeutic Strategies Network CRS

Rochester, New York, 14642, United States

Location

3201 Chapel Hill CRS

Chapel Hill, North Carolina, 27516, United States

Location

3203 Greensboro CRS

Greensboro, North Carolina, 27401, United States

Location

2401 Cincinnati CRS

Cincinnati, Ohio, 45267-0405, United States

Location

2951 The Miriam Hospital (TMH) ACTG CRS

Providence, Rhode Island, 02906, United States

Location

3652 Vanderbilt Therapeutics (VT) CRS

Nashville, Tennessee, 37204, United States

Location

31473 Houston AIDS Research Team (HART) CRS

Houston, Texas, 77030, United States

Location

5401 Puerto Rico AIDS Clinical Trials Unit CRS

San Juan, 00931, Puerto Rico

Location

MeSH Terms

Interventions

Isotretinoin

Intervention Hierarchy (Ancestors)

RetinoidsCarotenoidsPolyenesAlkenesHydrocarbons, AcyclicHydrocarbonsOrganic ChemicalsCyclohexenesCyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicTerpenesPigments, BiologicalBiological Factors

Results Point of Contact

Title
ACTG Clinicaltrials.gov Coordinator
Organization
ACTG Network Coordinating Center, Social and Scientific Systems, Inc.
ACTGCT.Gov@s-3.com
(301) 628-3313

Study Officials

  • Douglas Kwon, MD, PhD

    Massachusetts General Hospital

    STUDY CHAIR

  • Nina Lin, MD

    Harvard Medical School (HMS and HSDM)

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Masking Details
open label
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Participants were randomized 2:1 to Isotretinoin arm and no study treatment arm. The primary endpoints were compared between the 2 study arms.
Sponsor Type
NETWORK
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 21, 2013

First Posted

October 25, 2013

Study Start

July 2, 2014

Primary Completion

August 31, 2016

Study Completion

November 1, 2016

Last Updated

October 15, 2024

Results First Posted

September 5, 2017

Record last verified: 2024-10

Locations

PR(1)US(14)