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

Information source: AIDS Clinical Trials Group
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: HIV-1 Infection

Intervention: Isotretinoin (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: AIDS Clinical Trials Group

Official(s) and/or principal investigator(s):
Douglas Kwon, MD, PhD, Study Chair, Affiliation: Massachusetts General Hospital
Nina Lin, MD, Study Chair, Affiliation: Harvard Medical School

Summary

This phase II study is being done in HIV-infected subjects 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. Your immune system helps your body fight infections. When your immune system is not working well, you may be at greater risk for diseases that are common in aging, like heart disease, weaker bones, and kidney disease.

Clinical Details

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)

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Change from baseline in CD8+ T-cell activation at week 14/16

Secondary outcome:

Markers of gut microbial translocation

Markers of systemic inflammation and coagulation

Markers of macrophage activation (sCD163)

Peripheral CD4+ T-cell count

Th17 and Treg frequency

Cell-associated HIV-1 DNA and RNA

Endogenous retinoid metabolite profiles

Primary targeted adverse events

Pharmacokinetics - Trough concentrations of Isotretinoin and ART

Eligibility

Minimum age: 18 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 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: 1. Hemoglobin A1c (HgbA1c) levels ≤ 6. 5% 2. Hemoglobin ≥ 9. 0 g/dL 3. Platelet count ≥ 50,000/mm3 4. Creatinine ≤1. 5 mg/dl 5. CrCl ≥ 60 mL/min, calculated by the Cockcroft-Gault method 6. Aspartate aminotransferase (AST) (SGOT) ≤1. 5x upper limit of normal (ULN) 7. Alanine aminotransferase (ALT) (SGPT) ≤1. 5x ULN 8. Serum lipase ≤1. 5x ULN 9. Fasting triglyceride level ≤200 mg/dL 10. 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: 1. 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 2. 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: 1. 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. 2. 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. Exclusion Criteria:

- 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.

Locations and Contacts

5401 Puerto Rico AIDS Clinical Trials Unit CRS, San Juan 00931, Puerto Rico; Recruiting
Sylvia I. Davila Nieves, M.S., Phone: 787-767-9192, Email: sylvia.davila@upr.edu
Jorge L Santana-Bagur, MD, Principal Investigator

31788 Alabama CRS, Birmingham, Alabama 35294, United States; Recruiting
Karen G Savage, BSN, Phone: 205-996-2373
Edgar Overton, MD, Principal Investigator

601 University of California, Los Angeles CARE Center CRS, Los Angeles, California 90035, United States; Recruiting
Arezou Sadighi Akha, Phone: 310-206-6414
Raphael Landovitz, MD, Principal Investigator

801 University of California, San Francisco HIV/AIDS CRS, San Francisco, California 94110, United States; Recruiting
Jay Dwyer, RN, Phone: 415-514-0550, Ext: 354, Email: jdwyer@php.ucsf.edu
Diane V. Havlir, MD, Principal Investigator

101 Massachusetts General Hospital (MGH) CRS, Boston, Massachusetts 02114, United States; Recruiting
Teri Flynn, RN, ANP, MSN, Phone: 617-724-0072, Email: tflynn@partners.org
Rajesh Gandhi, MD, Principal Investigator

107 Brigham and Women's Hosp. ACTG CRS, Boston, Massachusetts 02115, United States; Recruiting
Cheryl Keenan, RN, Phone: 617-732-5635
Paul E. Sax, MD, Principal Investigator

2101 Washington University Therapeutics (WT) CRS, St. Louis, Missouri 63110, United States; Recruiting
Michael Klebert, RN, PhD, CANP, Phone: 314-454-0058, Email: mklebert@im.wustl.edu
David Clifford, MD, Principal Investigator

31786 New Jersey Medical School Clinical Research Center CRS, Newark, New Jersey 07103, United States; Recruiting
Janet Forcht, Phone: 973-972-1005, Email: janet.forcht@rutgers.edu
Shobha Swaminathan, MD, Principal Investigator

31787 University of Rochester Adult HIV Therapeutic Strategies Network CRS, Rochester, New York 14642, United States; Recruiting
Emily L. Cosimano, RN, Phone: 585-276-5903
Amneris Luque, MD, Principal Investigator

3201 Chapel Hill CRS, Chapel Hill, North Carolina 27516, United States; Recruiting
Susan Pedersen, RN, BSN, Phone: 919-966-6712
David A. Wohl, MD, Principal Investigator

3203 Greensboro CRS, Greensboro, North Carolina 27401, United States; Recruiting
Kim Epperson, RN, Phone: 336-832-7888, Email: kim.epperson@mosecone.com
Cornelius Van Dam, MD, Principal Investigator

2401 Cincinnati CRS, Cincinnati, Ohio 45267-0405, United States; Recruiting
Tammy Miller, RN, Phone: 513-584-8373
Carl Fichtenbaum, MD, Principal Investigator

2951 The Miriam Hospital (TMH) ACTG CRS, Providence, Rhode Island 02906, United States; Recruiting
Pamela Poethke, RN, Phone: 401-793-4396, Email: ppoethke@lifespan.org
Karen T. Tashima, MD, Principal Investigator

3652 Vanderbilt Therapeutics (VT) CRS, Nashville, Tennessee 37204, United States; Recruiting
Kyle Rybczyk, Phone: 615-936-2642
David W. Haas, MD, Principal Investigator

31473 Houston AIDS Research Team (HART) CRS, Houston, Texas 77030, United States; Recruiting
Maria Martinez, Phone: 713-500-6718
Roberto C. Arduino, MD, Principal Investigator

Additional Information

Starting date: July 2014
Last updated: August 5, 2015

Page last updated: August 23, 2015

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