Tripterygium Wilfordii Hook F (TwHF) Treatment for Immune Non-responders With HIV-1 Infection

NCT ID: NCT01666990

Last Updated: 2015-08-17

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-30
• Study Completion Date: 2016-12-31

Brief Summary

HIV-1 infection is characterized by progressive depletion of CD4+ T cells that eventually leads to clinically significant immunodeficiency. A chronic generalized immune activation is now being recognized to be the main driving force for T cell depletion, loss of anti-HIV-1 immunity and disease progression during chronic HIV-1 infection. However, it is still unknown whether reducing immune activation will restore CD4 T cell counts and leading to immune reconstitution in chronic HIV infection. Tripterygium Wilfordii Hook F (TwHF) has been demonstrated to decrease immune activation of the host, and can suppress inflammation in human diseases. Here, the investigators propose a hypothesis that TwHF can reduce immune over-activation which subsequently leads to the restoration of CD4 T-cell counts and immune reconstitution in HIV-infected immune non-responders.

Detailed Description

Although HIV-1 infection is characterized by progressive depletion of CD4+ T cells that eventually leads to clinically significant immunodeficiency, a chronic generalized immune activation is now being recognized to be the main driving force for T cell depletion, loss of anti-HIV-1 immunity and disease progression during chronic HIV-1 infection. In particular, this immune activation has been identified as a disease determinant independent of viral load or cell death in HIV-1 infection. A series of clinical evidences have indicated that activated CD8 T cells may attack body cells infected with viruses. Because of this, CD4 cells infected with HIV are frequently destroyed by CD8 cells.

In traditional Chinese medicine, extracts of the roots of the medicinal vine Tripterygium wilfordii Hook F (TwHF) (known in China as "lei gong teng" or "thunder god vine") have shown therapeutic promise in treating autoimmune and inflammatory conditions as well as cancer. In this extracts, three diterpenoids-triptolide, tripdiolide, and triptonide-are the most abundant and account for the immunosuppressive and anti-inflammatory effects observed in both in vitro and in vivo studies. Recently, different extracts of TwHF have been used in Chinese allopathic medicine for the treatment of autoimmune and inflammatory diseases, and small controlled trials reported good responses with TwHF extracts in patients with cadaveric kidney transplants and Crohn disease. In particular, a multicenter, double-blind, active comparator trial of a standardized TwHF extract in patients with active rheumatoid arthritis has shown a 20% improvement in American College of Rheumatology criteria in patients with TwHF than with sulfasalazine. Thus, TwHF may reduce inflammatory responses and promote tissue recovery in human diseases.

The purpose of this study is to learn whether and how well TwHF reduces the level of activation of CD8 cells in people infected with HIV. The decreased activation of CD8 cells may lead to a more CD4 T cell restoration and immune reconstitution in HIV infection. This study will also look at how well TwHF is tolerated and its safety in HIV- infected patients.

Participants in this study will be randomly assigned to one of two treatment arms:

Arm A: Participants will receive 48 weeks of TwHF treatment. Arm B: Participants will receive 48 weeks of placebo Study treatment will be given 20 mg, three times per day for a full 48 weeks. After treatment has started, participants will be asked to come to the clinic on Weeks 4, 8, 12, 16, 24, 36, and 48. At each visit participants will receive enough study treatment to last until the next visit. Each visit will last between 2 and 3 hours. At most visits participants will have a physical exam, answer questions about any medications they are taking and how they are feeling, and have blood drawn for safety to assess CD4/CD8 cell counts and viral load. Some additional blood will also be stored for immunology testing. At some visits participants will be asked questions about their medication and medical history, have pupils dilated, have a hearing test, and have an electrocardiogram (EKG). Some visits will require participants to arrive fasting. Pregnancy tests may also be conducted if the participant is able to become pregnant or if pregnancy is suspected.

Conditions

Human Immunodeficiency Virus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

TwHF, lifestyle counseling

Participants will receive TwHF (20mg each time, 3 times per day, for 48 weeks) from Day 0 through the Week 48 study visit.

Group Type: EXPERIMENTAL

TwHF

Intervention Type: DRUG

Taken oral, three times per day, at a dose of 20 mg/time for 48 weeks.

placebo, Lifestyle

Participants will receive placebo treatment (20mg each time, three times per day for 48 weeks) from Day 0 through the Week 48 study visit.

Group Type: PLACEBO_COMPARATOR

placebo treatment

Intervention Type: DRUG

Taken oral, three times per day, at a dose of 20 mg/time for 48 weeks.

Interventions

TwHF

Taken oral, three times per day, at a dose of 20 mg/time for 48 weeks.

Intervention Type: DRUG

placebo treatment

Taken oral, three times per day, at a dose of 20 mg/time for 48 weeks.

Intervention Type: DRUG

Other Intervention Names

treatment; placebo

Eligibility Criteria

Inclusion Criteria

1. HIV infected

2. antiretroviral therapy (ART) for at least 24 months prior to study entry and continue within the 12 months after study entry

3. CD4 count less than or equal to 250 cells/mm3 continuously before entry and at screening, obtained within 30 days prior to study entry

4. Viral load less than or equal to 400 copies/mL obtained within 30 days prior to study entry

5. Certain specified laboratory values obtained within 30 days prior to study entry. More information on this criterion can be found in the study protocol.

6. Documentation that pre-entry specimen for the primary immune activation endpoint responses has been obtained

7. No history of CDC category C AIDS-related opportunistic infections

8. Karnofsky performance score greater than or equal to 70 within 30 days prior to study entry

9. Ability and willingness to provide informed consent

Exclusion Criteria

1. Serious illness requiring systemic treatment and/or hospitalization within 30 days prior to study entry

2. Renal insufficiency, defined as serum creatinine greater than 1.5 mg/L, within 30 days prior to study entry

3. History of retinal disease

4. History of neoplasm other than localized squamous cell carcinoma of the skin

5. History of cardiac conduction abnormality or cardiomyopathy. More information on this criterion can be found in the study protocol.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing 302 Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fu-Sheng Wang, Professor

Role: PRINCIPAL_INVESTIGATOR

Beijing 302 Hospital

Locations

Beijing 302 Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

the Yunnan Hospital of Infectious Diseases

Kunming, Yunnan, China

Site Status: RECRUITING

Countries

China

Central Contacts

Zheng Zhang, Doctor

Role: CONTACT

zhangzheng1975@yahoo.com.cn

86-10-63879735

Facility Contacts

Zheng Zhang, Doctor

Role: primary

zhangzheng1975@yahoo.com.cn

86-10-63879735

Xicheng Wang, Doctor

Role: primary

wxch62597@21cn.com

86-0871-6256092

References

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

PMID: 18161758 (View on PubMed)

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Qiu D, Zhao G, Aoki Y, Shi L, Uyei A, Nazarian S, Ng JC, Kao PN. Immunosuppressant PG490 (triptolide) inhibits T-cell interleukin-2 expression at the level of purine-box/nuclear factor of activated T-cells and NF-kappaB transcriptional activation. J Biol Chem. 1999 May 7;274(19):13443-50. doi: 10.1074/jbc.274.19.13443.

Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Other Identifiers

Beijing302-007

Identifier Type: -

Identifier Source: org_study_id