Trial record 4 of 6 for:    Green Tea | NCCAM

Study to Evaluate Safety and Toxicity of Polyphenon E (EGCG) in HIV-1-Infected Individuals

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2011 by Baylor College of Medicine.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Christy Nance, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT01433289
First received: September 9, 2011
Last updated: September 12, 2011
Last verified: September 2011
  Purpose

The purpose of this study is to determine the safety, toxicity, dosing, and antiviral effects of epigallocatechin gallate (EGCG) in capsule form (Polyphenon® E), administered orally twice daily at three different doses in HIV-1-infected clinically stable, treatment-naïve and treatment-experienced adults not on concomitant antiretroviral (ARV) therapy.


Condition Intervention Phase
HIV Infection
Drug: Polyphenon E
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Placebo-Controlled, Dose-Blinded, Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics and Antiviral Activity of Polyphenon E (EGCG) as Monotherapy for 14 Days in Antiretroviral Naïve and Experienced, HIV-1-Infected Subjects

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • Number of Participants with Adverse Events [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
    Safety of Polyphenon E (800mg, 1200mg, 1600mg EGCG bid for 14 days)in HIV-1-infected subjects

  • Median change of log10 HIV-1 RNA [ Time Frame: 21 days ] [ Designated as safety issue: No ]
    Median change of log10 HIV-1 RNA from baseline in subjects who have completed 14 days of treatment (800mg, 1200mg, 1600mg EGCG bid)


Secondary Outcome Measures:
  • Proportion of participants achieving > 0.75 or 1.0 log10 reduction in HIV-1 RNA or <400 copies/ml [ Time Frame: 21 days ] [ Designated as safety issue: No ]
    Proportion of participants achieving >0.75 or 1.0 log10 reduction in HIV-1 RNA or <400 copies/ml with 14 days of Polyphenon E (800mg, 1200mg, or 1600mg EGCG bid).

  • The mean change in CD4+ T lymphocyte counts [ Time Frame: 21 days ] [ Designated as safety issue: No ]
    The mean change in CD4+ T lymphocyte counts when participants have had Polyphenon E (800mg, 1200mg, 1600mg EGCG bid for 14 days).

  • Composite of Pharmacokinetics Time Frame: predose, 0,0.5,1,1.5,2,3,4,6,8,12 hours post-dose [ Time Frame: 16 days ] [ Designated as safety issue: No ]
    Parameters will include area under the curve (AUC0-Τau), maximum concentration (Cmax), time to maximum concentration (Tmax), concentration at the end of the dosing interval (Ctr), oral clearance (CL/F), volume of distribution (Vd/F), and half-life (t1/2)


Estimated Enrollment: 24
Study Start Date: December 2010
Estimated Study Completion Date: July 2013
Estimated Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Polyphenon E 1600 mg/day
Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Four capsules twice a day.
Drug: Polyphenon E
There will be three treatment arms, each consisting of 8 participants. Two participants in each study arm will be randomized to receive placebo. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding arm will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each arm is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
Other Names:
  • EGCG
  • epigallocatechin gallate
  • green tea catechin
  • green tea extract
Experimental: Polyphenon E 2400 mg/day
Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Six capsules twice a day.
Drug: Polyphenon E
There will be three treatment arms, each consisting of 8 participants. Two participants in each study arm will be randomized to receive placebo. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding arm will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each arm is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
Other Names:
  • EGCG
  • epigallocatechin gallate
  • green tea catechin
  • green tea extract
Experimental: Polyphenon E 3200 mg/day
Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Eight capsules twice a day.
Drug: Polyphenon E
There will be three treatment arms, each consisting of 8 participants. Two participants in each study arm will be randomized to receive placebo. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding arm will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each arm is completed. It is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject.
Other Names:
  • EGCG
  • epigallocatechin gallate
  • green tea catechin
  • green tea extract

Detailed Description:

HIV-1 infection ultimately results in impaired specific immune function by virtue of the initial binding of the HIV-1 virion envelope glycoprotein 120 (gp120) to the CD4 receptor in complex with a chemokine receptor on the T-cell surface1. Even though gp120 elicits virus-neutralizing antibodies, HIV-1 eludes the immune system and leads to the onset of AIDS. Ever since the discovery of the virus as the causative agent, there has been an intense effort to develop therapeutic methods to inhibit or prevent infection.2-4 CD4, a cell surface glycoprotein expressed on T cells, plays an important role in the recognition of antigens by T cells and in their activation.5 It also acts as a receptor for HIV-1 as gp120 binds to it via its D1 domain and, uses this interaction to infect CD4+ T cells.5 Therefore, there has been interest in finding molecules that block the binding of gp120 to CD4 (entry inhibitors) as a way of reducing HIV-1 infectivity.

Studies have demonstrated evidence of high affinity binding of EGCG to the CD4 molecule with a Kd of 10nM with subsequent inhibition of gp120 binding to human CD4+ T cells. EGCG binds in the same molecular pocket on CD4, as does HIV-1-gp120 at physiologically relevant concentrations.

This is a phase I, placebo-controlled, dose-blinded, randomized study of Polyphenon® E as monotherapy in participants who are HIV-1-infected with a CD+ T lymphocyte count of at least 250 cells/mm3 and are ARV-naïve or ARV-experienced. There will be three treatment arms, each consisting of 8 evaluable participants. Two participants in each study arm will be randomized to receive placebo. Dosing will be escalated sequentially contingent on the safety profile of previous doses. Safety data from all participants receiving Polyphenon® E in the preceding arm will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each arm is completed. If at least 4 subjects on active drug in each arm have evaluable PK data, subjects will not be replaced. As the inability to achieve adequate EGCG concentrations that are necessary to inhibit HIV-1 replication is a major concern in this study, it is necessary to confirm EGCG pharmacokinetics in the event that the primary outcome measure of virologic response is not observed for each arm. For each PK visit on Study Days 1 and 14, a total of 10 blood samples will be obtained per subject. If only a few samples cannot be used (this depends on the individual subject's pharmacokinetic profile, although one or two unevaluable samples will not likely cause a subject's data to be unevaluable), PK analyses can still be performed and will not require subjects to be deemed unevaluable and replaced.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-infected individual as having at least two of the following in any combination obtained from 2 different samples: Positive HIV rapid test or ELISA and Western Blot; HIV RNA PCR>10,000 copies/ml; positive HIV DNA PCR; neutralizable HIV p 24 antigen
  • Asymptomatic HIV-1 infected individuals who are either antiretroviral-naive or treatment-experienced. Subjects must have not been on ARV treatment for at least 12 weeks prior to enrollment and not have plans to start ARV treatment within 8 weeks of study initiation.
  • Male or female 18 to 65 years of age. Males must use barrier methods of contraception Females must be willing to abide by protocol specified methods to avoid becoming pregnant. Women of childbearing potential must use an adequate form of birth control determined by the investigator (e.g., oral contraceptives, double-barrier methods, hormonal injectable or implanted contraceptives, tubal ligation, or vasectomy).
  • HIV-1 RNA >1,000 copies/mL at Screening.
  • In the opinion of the investigator, subject has a stable CD4+ T lymphocyte count while off ARV and 250 cells/mm3 at Screening.
  • Participants should have no clinically significant findings on screening evaluations (clinical, laboratory, or EKG).
  • Be able to comprehend and willing to sign an ICF.
  • Be able to comply with the protocol requirements.
  • Have life expectancy > 6 months.
  • Laboratory values obtained during screening must be within normal limits or meet the following requirements (Safety Labs):
  • ANC 1000/mm3
  • Hemoglobin 9.0 g/dL
  • Glucose (nonfasting) <116 mg/dL
  • Bilirubin 1.5 x upper limit of normal (ULN)
  • Liver function tests (AST & ALT) 1.25 x ULN at screening and baseline
  • GGT < 5.0 x ULN
  • Negative hepatitis panel obtained less than or equal to 6 months prior to Study Entry
  • Creatinine 1.3 x ULN
  • Creatine phosphokinase (CPK) 5 x ULN unless further evaluation determines it to be due to exercise
  • Urine protein 2+
  • Prothrombin time (PT)1.25 x ULN
  • Lipase 1.2 x ULN

Exclusion Criteria:

  • Current or recent (<3 months) history of opportunistic infection that,
  • Acute illness within 1 week of the baseline visit.
  • Participant is not able to comply with the dosing schedule and protocol evaluations.
  • Participant is anticipated to begin ARV treatment during participation in the study.
  • Pregnancy, breastfeeding or postpartum (less than 3 months).
  • Diagnosis of diabetes.
  • Any condition which could compromise participant safety or adherence to the protocol.
  • Documented positive test for hepatitis B surface antigen, hepatitis B surface antibody (with the exception of participants who received hepatitis B vaccination and have hepatitis B surface antibody), hepatitis B core antibody, and hepatitis C antibody.
  • Any grade 3 or 4 laboratory abnormality noted at screening according to the DAIDS grading scale (Appendix A), except for the following:
  • Grade 3 or 4 triglyceride elevations.
  • Grade 3 cholesterol elevation.
  • Grade 3 non-fasting glucose elevation.
  • Participant has a malabsorption syndrome possibly affecting drug absorption (e.g. Crohn's disease or chronic pancreatitis).
  • Participant has received an HIV prophylactic or therapeutic vaccination within 6 months prior to the first dose of study medication.
  • Investigational therapy within 30 days prior to the Baseline visit.
  • Radiation therapy or systemic cytotoxic chemotherapeutic agents within 12 weeks prior to the baseline visit or have not recovered from side effects from such therapy prior to the first dose of study medication.
  • Positive urine screen for drugs of abuse at Screening, unless the investigator deems that the result is associated with a prescribed medication or inhaled use of THC.
  • Inability to avoid all tea/tea products (including herbal, caffeinated, decaffeinated, iced tea), apples, chocolate, broad beans (fava beans), plums, prunes, cherries, fruit juices containing apples, cherries, or plums, dietary supplements, and herbal products for 1 week prior to the baseline visit and for the duration of the study.
  • Inability to limit caffeine intake to not exceed 12 oz. of caffeinated beverage per day (if espresso, no more than 1 oz. or 1 shot) beginning 2 days prior and for the duration of the study.
  • Prior exposure to TNX-355 (an investigational anti-HIV agent that binds to the CD4+ T lymphocyte surface).
  • Participant has used proton pump inhibitors starting 14 days before Study Day 1 and is unable to avoid taking proton pump inhibitors for the duration of the study.
  • Participant has used H2 blockers starting 24 hours before Study Day 1 and is unable to avoid taking H2 blockers for the duration of the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01433289

Contacts
Contact: Christina L Nance, PhD 832-824-2589 clnance@texaschildrens.org
Contact: Filiz O Seeborg, MD 832-824-1329 foseebor@texaschildrens.org

Locations
United States, Texas
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Christina L Nance, PhD    832-824-2589    clnance@texaschildrens.org   
Principal Investigator: Christina L Nance, PhD         
University of Texas Health Science Center Houston Recruiting
Houston, Texas, United States, 77030
Contact: Roberto C Arduino, MD    713-500-6731    roberto.c.arduino@uth.tmc.edu   
Sub-Investigator: Roberto C Arduino, MD         
Sponsors and Collaborators
Baylor College of Medicine
Investigators
Principal Investigator: Christina L Nance, PhD Baylor College of Medicine
Study Director: William T Shearer, MDPhD Baylor College of Medicine
  More Information

No publications provided

Responsible Party: Christy Nance, Assistant Professor, Pediatrics, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT01433289     History of Changes
Other Study ID Numbers: H-21490, R21AT004673
Study First Received: September 9, 2011
Last Updated: September 12, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Baylor College of Medicine:
HIV
safety
toxicity
pharmacokinetics
Polyphenon E
EGCG
green tea
CD4
viral load

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Epigallocatechin gallate
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Antimutagenic Agents
Anticarcinogenic Agents
Antineoplastic Agents
Therapeutic Uses
Neuroprotective Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 01, 2014