Bryostatin-1 Effect on HIV-1 Latency and Reservoir in HIV-1 Infected Patients Receiving Antiretroviral Treatment (BRYOLAT)

Bryostatin-1 Effect on HIV-1 Latency and Reservoir HIV-1 Infected Patients Receiving Antiretroviral Treatment: Pilot, Controlled, Double Blinded, Dose Searching Trial

Phase I, randomized, double blind, placebo-controlled, dose-finding trial. The trial´s goal is to evaluate two different doses of Bryostatin on HIV-1 latency and reservoir in HIV-1 infected patients receiving antiretroviral treatment.

Study Overview

• Status: Completed
• Conditions: HIV Infection
• Intervention / Treatment: Other: Placebo; Drug: Bryostatin 1 (10ug/m2); Drug: Bryostatin 1 (20ug/m2)

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Non US/Canada
    • Madrid, Non US/Canada, Spain, 28034
      • Infectious Diseases Service

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients understanding the trial purpose
• Patients between 18 and 50 years of age
• Patients with chronic HIV-1 infection
• Patients receiving antiretroviral treatment with at least 3 active drugs for at least 2 years
• Undetectable viral load measured by ultra sensitive methods
• CD4+ levels higher than 350 cells/mm3
• Patients committed to use contraceptive methods during the trial and up to 3 months after.

Exclusion Criteria:

• Previous antiretroviral treatment failure, as any viral load outbreak after having had undetectable HIV-1 load. Low grade, transitory outbreaks (<200 RNA copies/ml) resolved without treatment modifications are excluded
• Patients planned to interrupt antiretroviral treatment during the trial
• Patients receiving immunosuppressant or immunostimulant drugs, including valproic acid.
• Pregnant women
• Bryostatin-1 hypersensitivity
• Being enrolled in another clinical trial or having participated in another clinical trial in the previous 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Group 1; Patients receiving placebo (sodium chloride) at single dose	Other: Placebo; Group 1: Placebo (sodium chloride 0.8 %) at single dose
Active Comparator: Group 2; Patients receiving Bryostatin 1 (10ug/m2) at single dose	Drug: Bryostatin 1 (10ug/m2); Group 2: Bryostatin 1 (10ug/m2) at single dose
Active Comparator: Group 3; Patients receiving Bryostatin 1 (20ug/m2) at single dose	Drug: Bryostatin 1 (20ug/m2); Group 3: Bryostatin 1 (20ug/m2) at single dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Intracellular HIV-1 RNA (usRNA and msRNA) level before and after bryostatin-1 administration	Baseline visit and days 2 and 3 after the day of treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
HIV-1 RNA level	Baseline visit, day 0 (15, 30, 60 minutes after begining of drug administration and 1, 2, 4, 8, 12 hours after begining of drug administration) and days 1, 2 and 3
CD4+ and CD8+ T (CD38+ and HLA DR+ positive) cell level	Baseline visit, day 1 and day 3
Episomal DNA with 2 LTRs level	Baseline visit, day 1 and day 3
Adverse Events	From baseline visit to day 28 after drug administration

Collaborators and Investigators

• Sponsor: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
• Investigators: Principal Investigator: Santiago Moreno, MD, PhD, Hospital Universitario Ramon y Cajal

Publications and helpful links

General Publications

• Persaud D, Zhou Y, Siliciano JM, Siliciano RF. Latency in human immunodeficiency virus type 1 infection: no easy answers. J Virol. 2003 Feb;77(3):1659-65. doi: 10.1128/jvi.77.3.1659-1665.2003. No abstract available.
• Blankson JN, Gallant JE, Quinn TC, Bartlett JG, Siliciano RF. Loss of HIV-1-specific immunity during treatment interruption in 2 chronically infected patients. JAMA. 2002 Jul 10;288(2):162-4. doi: 10.1001/jama.288.2.162-a. No abstract available.
• Richman DD, Margolis DM, Delaney M, Greene WC, Hazuda D, Pomerantz RJ. The challenge of finding a cure for HIV infection. Science. 2009 Mar 6;323(5919):1304-7. doi: 10.1126/science.1165706.
• Gutierrez C, Serrano-Villar S, Madrid-Elena N, Perez-Elias MJ, Martin ME, Barbas C, Ruiperez J, Munoz E, Munoz-Fernandez MA, Castor T, Moreno S. Bryostatin-1 for latent virus reactivation in HIV-infected patients on antiretroviral therapy. AIDS. 2016 Jun 1;30(9):1385-92. doi: 10.1097/QAD.0000000000001064.

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: October 16, 2014
• First Submitted That Met QC Criteria: October 20, 2014
• First Posted (Estimate): October 21, 2014

Study Record Updates

• Last Update Posted (Estimate): December 18, 2015
• Last Update Submitted That Met QC Criteria: December 17, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: HIV reservoir; Bryostatin
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Adjuvants, Immunologic; Bryostatin 1
• Other Study ID Numbers: BRYOLAT