HIV-1 InfectionPhase 2NCT01969058
Effect of Isotretinoin on Immune Activation Among HIV-1 Infected Subjects With Incomplete CD4+ T Cell Recovery
A Phase 2 study testing Isotretinoin in people with HIV-1 Infection, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 15 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- HIV-1 Infection
- What is being tested?
- Isotretinoin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- 15 sitesin 2 countries
- Study dates
- 2 Jul 2014to Nov 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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
- CrCl ≥ 60 mL/min, calculated by the Cockcroft-Gault method
- Aspartate aminotransferase (AST) (SGOT) ≤1.5x upper limit of normal (ULN)
- Alanine aminotransferase (ALT) (SGPT) ≤1.5x ULN
- Serum lipase ≤1.5x ULN
- Fasting triglyceride level ≤200 mg/dL
- Fasting glucose <126mg/dL
- Karnofsky performance score >/=70 within 30 days prior to entry.
- Men and post-menopausal females aged ≥ 18 years and ≤ 80 years at entry.
- Note: Post-menopausal is defined as having either:
- Appropriate medical documentation (see note) of prior complete bilateral oophorectomy (i.e., surgical removal of the ovaries, resulting in "surgical menopause" and occurring at the age at which the procedure was performed), OR
- Permanent cessation (12 consecutive months or more of amenorrhea) of previously occurring menses as a result of ovarian failure with documentation of hormonal deficiency by a certified healthcare provider (i.e., "spontaneous menopause").
- Hormonal deficiency should be properly documented (see note) in the case of suspected spontaneous menopause as follows:
- If age >54 years and with the absence of normal menses: Serum FSH (Follicle Stimulating Hormone) level elevated to within the post-menopausal range based on the laboratory reference range where the hormonal assay is performed.
- If age ≤ 54 years and with the absence of normal menses: Negative serum or urine HCG with concurrently elevated serum FSH (follicle stimulating hormone) level in the post-menopausal range, depressed estradiol (E2) level in the post-menopausal range, and absent serum progesterone level, based on the laboratory reference ranges where the hormonal assays are performed.
- NOTE: "Appropriate documentation", and "properly documented" means written documentation or oral communication from a clinician or clinician's staff documented in source documents of an operative report, discharge summary, or
- No active hepatitis B or C infection. NOTE: For subjects who have documentation of prior infection, but no active hepatitis infection, evidence of clearance must be greater than 1 year.
- Ability and willingness of subject to provide informed consent.
- Willingness to adhere to the iPLEDGE program requirements.
- Indication of willingness to participate in the substudy A5330s. NOTE: In the event that 12 or fewer subjects have enrolled into A5330s by the time enrollment in the main study has reached 50% of the accrual target, A5330s enrollment will be required.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
15 sites in 2 countries.
15 sites in 2 countries
United States14 sites
31788 Alabama CRS
Birmingham, Alabama, 35294
101 Massachusetts General Hospital (MGH) CRS
Boston, Massachusetts, 02114
107 Brigham and Women's Hosp. ACTG CRS
Boston, Massachusetts, 02115
3201 Chapel Hill CRS
Chapel Hill, North Carolina, 27516
2401 Cincinnati CRS
Cincinnati, Ohio, 45267-0405
3203 Greensboro CRS
Greensboro, North Carolina, 27401
31473 Houston AIDS Research Team (HART) CRS
Houston, Texas, 77030
601 University of California, Los Angeles CARE Center CRS
Los Angeles, California, 90035
3652 Vanderbilt Therapeutics (VT) CRS
Nashville, Tennessee, 37204
31786 New Jersey Medical School Clinical Research Center CRS
Newark, New Jersey, 07103
2951 The Miriam Hospital (TMH) ACTG CRS
Providence, Rhode Island, 02906
31787 University of Rochester Adult HIV Therapeutic Strategies Network CRS
Rochester, New York, 14642
801 University of California, San Francisco HIV/AIDS CRS
San Francisco, California, 94110
2101 Washington University Therapeutics (WT) CRS
St Louis, Missouri, 63110
Puerto Rico1 site
5401 Puerto Rico AIDS Clinical Trials Unit CRS
San Juan, 00931
About this study
Official title: A Prospective Randomized Controlled Study to Evaluate the Effect of Isotretinoin on Immune Activation Among HIV-1 Infected Subjects With Incomplete CD4+ T Cell Recovery on Suppressive Antiretroviral Therapy (ART)
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.
Read the detailed description
Isotretinoin was administered to participants in the Isotretinoin arm at approximately 0.5 mg/kg PO once daily for 4 weeks, then increased to approximately 1.0 mg/kg PO once daily for 12 weeks. Follow-up continues to week 28 to evaluate the duration of effect. Randomization was stratified by willingness to participate in the gut biopsy substudy, A5330s. The study population included HIV-1 infected adults whose virus was suppressed on ART, excluding women of child bearing potential.
- Conditions
- HIV-1 Infection
- Being tested
- Isotretinoin
- Keywords
- Isotretinoin, HIV-1, immunology markers, immune activation, viral suppression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IsotretinoinDrug
Also called 13-cis-retinoic acid
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Isotretinoin |
| No study treatment Arm | No intervention | No Isotretinoin treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: baseline, week 14/16
Secondary outcomes (20)
Change in CD8+ T-cell Activation
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 week 14/16 to week 28 (week 28 - week 14/16) and from baseline to week 28 (week 28 - baseline).
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.
Measured: baseline, week 14/16, week 28
Change in sCD14
sCD14 (soluble cluster of differentiation 14) is a marker of gut microbial translocation and monocyte activation.
The outcome measures are changes in log10 transformed sCD14 from baseline to week 14/16 (week 14/16 - baseline), from week 14/16 to week 28 (week 28 - week 14/16), and from baseline to week 28 (week 28 - baseline).
Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 14 and week 16 were averaged for week 14/16.
Measured: baseline, week 14/16, week 28
Change in I-FABP
I-FABP (intestinal-fatty acid binding protein) is a marker of intestinal cell damage and turnover.
The outcome measures are changes in log10 transformed I-FABP from baseline to week 14/16 (week 14/16 - baseline), from week 14/16 to week 28 (week 28 - week 14/16), and from baseline to week 28 (week 28 - baseline).
Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 14 and week 16 were averaged for week 14/16.
Measured: baseline, week 14/16, week 28
Change in IL-6
IL-6 (Interleukin-6) is a marker of systemic inflammation. The outcome measures are changes in log10 transformed IL-6 from baseline to week 14/16 (week 14/16 - baseline), from week 14/16 to week 28 (week 28 - week 14/16), and from baseline to week 28 (week 28 - baseline).
Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 14 and week 16 were averaged for week 14/16.
Measured: baseline, week 14/16, week 28
Change in hsCRP
hsCRP (high-sensitivity C-reactive protein) is a marker of inflammation. Change in log10 transformed hsCRP from baseline to week 14/16 (week 14/16 - baseline), from week 14/16 to week 28 (week 28 - week 14/16), and from baseline to week 28 (week 28 - baseline).
Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 14 and week 16 were averaged for week 14/16.
Measured: baseline, week 14/16, week 28
Change in sTNF-r1
sTNF-r1 (soluble tumour necrosis alpha receptor 1) is a marker of inflammation. Change in log10 transformed sTNF-r1 from baseline to week 14/16 (week 14/16 - baseline), from week 14/16 to week 28 (week 28 - week 14/16), and from baseline to week 28 (week 28 - baseline).
Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 14 and week 16 were averaged for week 14/16.
Measured: baseline, week 14/16, week 28
Change in sTNF-r2
sTNF-r2 (soluble tumour necrosis alpha receptor 2) is a marker of inflammation. Change in log10 transformed sTNF-r2 from baseline to week 14/16 (week 14/16 - baseline), from week 14/16 to week 28 (week 28 - week 14/16), and from baseline to week 28 (week 28 - baseline).
Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 14 and week 16 were averaged for week 14/16.
Measured: baseline, week 14/16, week 28
Change in D-dimer
D-dimer (or D dimer) is a marker of coagulation activation. Change in log10 transformed D-dimer from baseline to week 14/16 (week 14/16 - baseline), from week 14/16 to week 28 (week 28 - week 14/16), and from baseline to week 28 (week 28 - baseline).
Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 14 and week 16 were averaged for week 14/16.
Measured: baseline, week 14/16, week 28
Change in TF
TF (Tissue Factor) is a marker of Coagulation. Change in log10 transformed TF from baseline to week 14/16 (week 14/16 - baseline), from week 14/16 to week 28 (week 28 - week 14/16), and from baseline to week 28 (week 28 - baseline).
Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 14 and week 16 were averaged for week 14/16.
Measured: baseline, week 14/16, week 28
Change in sCD163
sCD163 (soluble CD 163) is a marker of macrophage activation Change in log10 transformed sCD163 from baseline to week 14/16 (week 14/16 - baseline), from week 14/16 to week 28 (week 28 - week 14/16), and from baseline to week 28 (week 28 - baseline).
Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 14 and week 16 were averaged for week 14/16.
Measured: baseline, week 14/16, week 28
Change in CD4+ T-cell Count
Change in peripheral total CD4 cell count from baseline to week 14/16 (week 14/16 - baseline), from week 14/16 to week 28 (week 28 - week 14/16), and from baseline to week 28 (week 28 - baseline).
Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 14 and week 16 were averaged for week 14/16.
Measured: baseline, week 14/16, week 28
Change in Cell-associated HIV-1 RNA
Cell-associated HIV-1 RNA in blood from baseline to week 14/16(week 14/16 - baseline), from week 14/16 to week 28 (week 28 - week 14/16), and from baseline to week 28 (week 28 - baseline).
Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 14 and week 16 were averaged for week 14/16.
For cell-associated HIV-1 RNA results below the assay limit, the lowest value of the sample was imputed to these results (1.32 log10 copies/10^6 CD4 cells).
Since there are only a few results below the assay limit, it is still reasonable to summarize the absolute changes for cell-associated HIV-1 RNA, where changes were calculated based on the imputed values (described above) for below assay limit results.
Measured: baseline, week 14/16, week 28
Cell-associated HIV-1 DNA
Cell-associated HIV-1 DNA in blood at baseline, week 14/16, and week 28. Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 14 and week 16 were averaged for week 14/16.
For cell-associated HIV-1 DNA results below the assay limit, the lowest value of the sample was imputed to these results and considered lowest ranks (1.62 log10 copies/10^6 CD4 cells).
It was originally planned to summarize the absolute changes for cell-associated HIV-1 DNA. However, since there are many results below limit of detection, analyzing the absolute changes would be inappropriate in this case.
Instead, the baseline, week 14/16, and week 28 levels were summarized.
Measured: baseline, week 14/16, week 28
Change in Treg Frequency (%FoxP3+/CD25hi+/CD39+/CD127-(CD4+))
Treg (T Regulatory) Cells are a subpopulation of T cells which modulate the immune system.
The outcome measure is the change in percent FoxP3+/CD25hi+/CD39+/CD127-(CD4+) from baseline to week 14/16 (week 14/16 - baseline), from week 14/16 to week 28 (week 28 - week 14/16), and from baseline to week 28 (week 28 - baseline).
Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 14 and week 16 were averaged for week 14/16.
Measured: baseline, week 14/16, week 28
Change in Th17 Frequency (%IFNg-/IL17+(CD161+/CCR6+))
Th17 (T-helper 17) cells are a subset of pro-inflammatory T helper cells defined by their production of interleukin 17 (IL-17).
The outcome is the change in percent IFNg-/IL17+(CD161+/CCR6+) from baseline to week 14/16 (week 14/16 - baseline), from week 14/16 to week 28 (week 28 - week 14/16), and from baseline to week 28 (week 28 - baseline).
Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 14 and week 16 were averaged for week 14/16.
Measured: baseline, week 14/16, week 28
Pharmacokinetics - Endogenous Levels of Retinoid Metabolites for Isotretinoin Arm
Isotretinoin Arm (Arm A) only. Endogenous retinoid metabolites are defined as the average concentrations of Retinol, and Total Retinyl Ester from weeks 0, 20, and 28.
Measured: weeks 0, 20, 28
Pharmacokinetics - Steady-state Trough Concentrations of Isotretinoin for Isotretinoin Arm
Isotretinoin arm (Arm A) only, steady-state trough concentrations of Isotretinoin is defined as the average of 'eligible' concentrations at weeks 8, 12, and 16, where 'eligible' means the time from the previous dose to the blood draw of the sample must have been in the 14-to-30 hour range, and the participant must have taken at least 3 doses in the prior 4 days.
Measured: weeks 8, 12, 16
Pharmacokinetics - Trough Concentrations of TDF for Isotretinoin Arm
Isotretinoin arm (Arm A) only, trough concentrations of TDF (Tenofovir) is defined as the average of 'eligible' concentrations, where 'eligible' means the time from the previous dose to the blood draw of the sample must have been in the 20-to-28 hour range, and the participant must have taken at least 3 doses in the prior 4 days.
TDF trough during Isotretinoin administration is the average of 'eligible' concentrations from weeks 8, 12, and 16; TDF trough without Isotretinoin administration is the average of 'eligible' concentrations from weeks 0 and 20.
(Week 28 data is not available.)
Measured: weeks 0, 8, 12, 16, 20
Pharmacokinetics - 12-hour Levels of EFV for Isotretinoin Arm
Isotretinoin arm (Arm A) only, 12-hour levels of EFV (Efavirenz) is defined as the average of 'eligible' concentrations, where 'eligible' means the time from the previous dose to the blood draw of the sample must have been in the 9-to-15 hour range, and the participant must have taken at least 3 doses in the prior 4 days.
EFV trough during Isotretinoin administration is the average of 'eligible' concentrations from weeks 8, 12, and 16; EFV trough without Isotretinoin administration is the average of 'eligible' concentrations from weeks 0 and 20.
(Week 28 data is not available.)
Measured: weeks 0, 8, 12, 16, 20
Primary Targeted Adverse Events
Targeted events for A5325 include: events that meet the International Conference on Harmonization (ICH) definitions for a serious adverse event, post-entry signs/symptoms and laboratory abnormalities of Grade ≥3 or that lead to a change in treatment regardless of grade, and any diagnoses.
Measured: from study entry to end of study (week 28)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2013 (estimated)
- Study start2 Jul 2014
- Primary completion31 Aug 2016
- Study completionNov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIV-1 InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants were randomized 2:1 to Isotretinoin arm and no study treatment arm. The primary endpoints were compared between the 2 study arms.
- Masking
- None (open label)
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Douglas Kwon, MD, PhD, Study chair, Massachusetts General HospitalNina Lin, MD, Study chair, Harvard Medical School (HMS and HSDM)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01969058
- Sponsor's protocol ID
- ACTG A5325
- Other IDs
- UM1AI068636
- Status last verified
- Oct 2024
- First submitted
- 21 Aug 2013
- Last updated
- 15 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Randomized Controlled Study to Evaluate the Effect of Isotretinoin on Immune Activation Among HIV-1 Infected Subjects With Incomplete CD4+ T Cell Recovery on Suppressive Antiretroviral Therapy (ART)
- ClinicalTrials.gov ID
- NCT01969058
- Acronym / sponsor ID
- ACTG A5325
- Conditions
- HIV-1 Infection
- Keywords
- Isotretinoin, HIV-1, immunology markers, immune activation, viral suppression
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- Advancing Clinical Therapeutics Globally for HIV/AIDS and Other InfectionsResearch network
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- 2 Jul 2014 (actual)
- Primary completion
- 31 Aug 2016 (actual)
- Study completion
- Nov 2016 (actual)
- First posted
- 25 Oct 2013 (estimated)
- Results
- Posted 5 Sep 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Isotretinoin was administered to participants in the Isotretinoin arm at approximately 0.5 mg/kg PO once daily for 4 weeks, then increased to approximately 1.0 mg/kg PO once daily for 12 weeks. Follow-up continues to week 28 to evaluate the duration of effect. Randomization was stratified by willingness to participate in the gut biopsy substudy, A5330s. The study population included HIV-1 infected adults whose virus was suppressed on ART, excluding women of child bearing potential.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Participants were randomized 2:1 to Isotretinoin arm and no study treatment arm. The primary endpoints were compared between the 2 study arms.
| Arm | Type | Receives |
|---|---|---|
| Isotretinoin Arm | Active comparator | Drug: IsotretinoinParticipants 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 intervention | –No Isotretinoin treatment |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (34 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IsotretinoinAlso: 13-cis-retinoic acidIsotretinoin 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. | Drug | Isotretinoin Arm |
Primary outcome
Change in CD8+ T-cell Activation From Baseline to Week 14/16
Time frame: baseline, 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).
20 secondary outcomes
Change in CD8+ T-cell Activation
Time frame: baseline, week 14/16, week 28
Change in sCD14
Time frame: baseline, week 14/16, week 28
Change in I-FABP
Time frame: baseline, week 14/16, week 28
Change in IL-6
Time frame: baseline, week 14/16, week 28
Change in hsCRP
Time frame: baseline, week 14/16, week 28
Change in sTNF-r1
Time frame: baseline, week 14/16, week 28
Change in sTNF-r2
Time frame: baseline, week 14/16, week 28
Change in D-dimer
Time frame: baseline, week 14/16, week 28
Change in TF
Time frame: baseline, week 14/16, week 28
Change in sCD163
Time frame: baseline, week 14/16, week 28
Change in CD4+ T-cell Count
Time frame: baseline, week 14/16, week 28
Change in Cell-associated HIV-1 RNA
Time frame: baseline, week 14/16, week 28
Cell-associated HIV-1 DNA
Time frame: baseline, week 14/16, week 28
Change in Treg Frequency (%FoxP3+/CD25hi+/CD39+/CD127-(CD4+))
Time frame: baseline, week 14/16, week 28
Change in Th17 Frequency (%IFNg-/IL17+(CD161+/CCR6+))
Time frame: baseline, week 14/16, week 28
Pharmacokinetics - Endogenous Levels of Retinoid Metabolites for Isotretinoin Arm
Time frame: weeks 0, 20, 28
Pharmacokinetics - Steady-state Trough Concentrations of Isotretinoin for Isotretinoin Arm
Time frame: weeks 8, 12, 16
Pharmacokinetics - Trough Concentrations of TDF for Isotretinoin Arm
Time frame: weeks 0, 8, 12, 16, 20
Pharmacokinetics - 12-hour Levels of EFV for Isotretinoin Arm
Time frame: weeks 0, 8, 12, 16, 20
Primary Targeted Adverse Events
Time frame: from study entry to end of study (week 28)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Douglas Kwon, MD, PhD study chair
Massachusetts General Hospital
Nina Lin, MD study chair
Harvard Medical School (HMS and HSDM)
15 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Isotretinoin in people with HIV-1 Infection, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 15 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 34 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in CD8+ T-cell Activation From Baseline to Week 14/16 (time frame: baseline, week 14/16). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2024.