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

NCT01433289 | Completed Phase 1 Results DMC

• 2 other identifiers: H-21490R21AT004673
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

HIV Infection

Keywords

HIV; safety; toxicity; pharmacokinetics; Polyphenon E; EGCG; green tea; CD4; viral load

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Adverse Events

  Safety of Polyphenon E (800mg, 1200mg, 1600mg EGCG twice daily for 14 days) in HIV-1-infected subjects.

  14 days

• Median Change of log10 HIV-1 RNA Copies/ml

  Median change of log10 HIV-1 RNA copies/ml from baseline in subjects who have completed 14 days of treatment (800mg, 1200mg, 1600mg EGCG bid) or placebo.

  Baseline and 14 days

Secondary Outcomes (3)

• Number of Participants Achieving > 0.75 or 1.0 log10 Reduction in HIV-1 RNA or <400 Copies/ml

  Baseline to 14 days

• The Mean Change in CD4+ T Lymphocyte Counts

  Baseline to 14 days

• Composite of Pharmacokinetics Time Frame: Predose, 0,0.5,1,1.5,2,3,4,6,8,12 Hours Post-dose

  Predose, 0,0.5,1,1.5,2,3,4,6,8,12 Hours Post-dose on Days 1 and 14

Study Arms (4)

Polyphenon E 1600 mg/day

EXPERIMENTAL

Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Four capsules twice a day.

Drug: Polyphenon E

Polyphenon E 2400 mg/day

EXPERIMENTAL

Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Six capsules twice a day.

Drug: Polyphenon E

Polyphenon E 3200 mg/day

EXPERIMENTAL

Drug: Polyphenon E Polyphenon E capsules containing 200 mg of epigallocatechin-gallate. Eight capsules twice a day.

Drug: Polyphenon E

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Polyphenon E DRUG

There will be 3 dose levels and for each dose level, there will be 6 subjects who will receive the study drug and 2 subjects who will be randomized to take 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 dose level will be evaluated and considered acceptable prior to escalation to the next higher dose. PK analyses will be also performed as each dose level 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.

Also known as: EGCG, epigallocatechin gallate, green tea catechin, green tea extract

Polyphenon E 1600 mg/day; Polyphenon E 2400 mg/day; Polyphenon E 3200 mg/day

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• National Center for Complementary and Integrative Health (NCCIH): collaborator

Study Sites (2)

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center Houston

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

HIV Infections

Interventions

polyphenon E; epigallocatechin gallate; Tea

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Plant Preparations; Biological Products; Complex Mixtures; Beverages; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Results Point of Contact

• Title: Supriya Parikh
• Organization: Baylor

supriya.parikh@bcm.edu

832-824-2589

Study Officials

• Filiz Seeborg, MD, MPH

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

• Roberto Arduino, MD

  The University of Texas Health Science Center, Houston

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor Pediatrics

Study Record Dates

• First Submitted: September 9, 2011
• First Posted: September 13, 2011
• Study Start: December 1, 2010
• Primary Completion: August 1, 2014
• Study Completion: July 1, 2015
• Last Updated: May 19, 2023
• Results First Posted: May 19, 2023

Record last verified: 2023-04

Locations

US (2)