NCT01666990

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
60

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Jun 2012

Longer than P75 for phase_1

Geographic Reach
1 country

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2012

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

August 15, 2012

Completed
2 days until next milestone

First Posted

Study publicly available on registry

August 17, 2012

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2016

Completed
Last Updated

August 17, 2015

Status Verified

August 1, 2015

Enrollment Period

4.5 years

First QC Date

August 15, 2012

Last Update Submit

August 14, 2015

Conditions

Human Immunodeficiency Virus

Keywords

Tripterygium wilfordii Hook F (TwHF)HIVCD4immune over-activation

Outcome Measures

Primary Outcomes (1)

  • the total CD4 T cell counts compared with CD4 T cell counts at baseline

    At Baseline and at week 4, 8, 12, 24, 36 and 48

Secondary Outcomes (17)

  • the CD38 expression on CD8 T cells

    At Baseline and at week 4, 8, 12, 24, 36 and 48

  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability

    at baseline and up to week 48

  • plasma RNA copies/mL

    At Entry and at week 12 , 24 and 48

  • the ratio of CD4 and CD8 T cells

    At baseline and at week 4, 8, 12, 24, 36 and 48

  • the total cell counts of peripheral CD3 T cells

    At baseline and at week 4, 8, 12, 24, 36 and 48

  • +12 more secondary outcomes

Study Arms (2)

TwHF, lifestyle counseling

EXPERIMENTAL

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

Drug: TwHF

placebo, Lifestyle

PLACEBO COMPARATOR

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

Drug: placebo treatment

Interventions

TwHFDRUG

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

Also known as: treatment
TwHF, lifestyle counseling
placebo treatmentDRUG

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

Also known as: placebo
placebo, Lifestyle

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • HIV infected
  • antiretroviral therapy (ART) for at least 24 months prior to study entry and continue within the 12 months after study entry
  • CD4 count less than or equal to 250 cells/mm3 continuously before entry and at screening, obtained within 30 days prior to study entry
  • Viral load less than or equal to 400 copies/mL obtained within 30 days prior to study entry
  • Certain specified laboratory values obtained within 30 days prior to study entry. More information on this criterion can be found in the study protocol.
  • Documentation that pre-entry specimen for the primary immune activation endpoint responses has been obtained
  • No history of CDC category C AIDS-related opportunistic infections
  • Karnofsky performance score greater than or equal to 70 within 30 days prior to study entry
  • Ability and willingness to provide informed consent

You may not qualify if:

  • Serious illness requiring systemic treatment and/or hospitalization within 30 days prior to study entry
  • Renal insufficiency, defined as serum creatinine greater than 1.5 mg/L, within 30 days prior to study entry
  • History of retinal disease
  • History of neoplasm other than localized squamous cell carcinoma of the skin
  • History of cardiac conduction abnormality or cardiomyopathy. More information on this criterion can be found in the study protocol.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Beijing 302 Hospital

Beijing, Beijing Municipality, 100039, China

RECRUITING

the Yunnan Hospital of Infectious Diseases

Kunming, Yunnan, 650301, China

RECRUITING

Related Publications (10)

  • Hammer SM, Squires KE, Hughes MD, Grimes JM, Demeter LM, Currier JS, Eron JJ Jr, Feinberg JE, Balfour HH Jr, Deyton LR, Chodakewitz JA, Fischl MA. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team. N Engl J Med. 1997 Sep 11;337(11):725-33. doi: 10.1056/NEJM199709113371101.

    PMID: 9287227BACKGROUND

  • Mocroft A, Vella S, Benfield TL, Chiesi A, Miller V, Gargalianos P, d'Arminio Monforte A, Yust I, Bruun JN, Phillips AN, Lundgren JD. Changing patterns of mortality across Europe in patients infected with HIV-1. EuroSIDA Study Group. Lancet. 1998 Nov 28;352(9142):1725-30. doi: 10.1016/s0140-6736(98)03201-2.

    PMID: 9848347BACKGROUND

  • Appay V, Sauce D. Immune activation and inflammation in HIV-1 infection: causes and consequences. J Pathol. 2008 Jan;214(2):231-41. doi: 10.1002/path.2276.

    PMID: 18161758BACKGROUND

  • Li T, Wu N, Dai Y, Qiu Z, Han Y, Xie J, Zhu T, Li Y. Reduced thymic output is a major mechanism of immune reconstitution failure in HIV-infected patients after long-term antiretroviral therapy. Clin Infect Dis. 2011 Nov;53(9):944-51. doi: 10.1093/cid/cir552. Epub 2011 Sep 29.

    PMID: 21960716BACKGROUND

  • Goldbach-Mansky R, Wilson M, Fleischmann R, Olsen N, Silverfield J, Kempf P, Kivitz A, Sherrer Y, Pucino F, Csako G, Costello R, Pham TH, Snyder C, van der Heijde D, Tao X, Wesley R, Lipsky PE. Comparison of Tripterygium wilfordii Hook F versus sulfasalazine in the treatment of rheumatoid arthritis: a randomized trial. Ann Intern Med. 2009 Aug 18;151(4):229-40, W49-51. doi: 10.7326/0003-4819-151-4-200908180-00005.

    PMID: 19687490BACKGROUND

  • Kupchan SM, Court WA, Dailey RG Jr, Gilmore CJ, Bryan RF. Triptolide and tripdiolide, novel antileukemic diterpenoid triepoxides from Tripterygium wilfordii. J Am Chem Soc. 1972 Oct 4;94(20):7194-5. doi: 10.1021/ja00775a078. No abstract available.

    PMID: 5072337BACKGROUND

  • Ji SM, Wang QW, Chen JS, Sha GZ, Liu ZH, Li LS. Clinical trial of Tripterygium Wilfordii Hook F. in human kidney transplantation in China. Transplant Proc. 2006 Jun;38(5):1274-9. doi: 10.1016/j.transproceed.2006.03.017.

    PMID: 16797280BACKGROUND

  • Tao X, Lipsky PE. The Chinese anti-inflammatory and immunosuppressive herbal remedy Tripterygium wilfordii Hook F. Rheum Dis Clin North Am. 2000 Feb;26(1):29-50, viii. doi: 10.1016/s0889-857x(05)70118-6.

    PMID: 10680192BACKGROUND

  • 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.

    PMID: 10224109BACKGROUND

  • Tao X, Schulze-Koops H, Ma L, Cai J, Mao Y, Lipsky PE. Effects of Tripterygium wilfordii hook F extracts on induction of cyclooxygenase 2 activity and prostaglandin E2 production. Arthritis Rheum. 1998 Jan;41(1):130-8. doi: 10.1002/1529-0131(199801)41:13.0.CO;2-4.

    PMID: 9433878BACKGROUND

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Therapeutics

Condition Hierarchy (Ancestors)

HIV InfectionsBlood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesSlow Virus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Study Officials

  • Fu-Sheng Wang, Professor

    Beijing 302 Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Zheng Zhang, Doctor

CONTACT

86-10-63879735zhangzheng1975@yahoo.com.cn

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, CARE PROVIDER
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 15, 2012

First Posted

August 17, 2012

Study Start

June 1, 2012

Primary Completion

December 1, 2016

Study Completion

December 1, 2016

Last Updated

August 17, 2015

Record last verified: 2015-08

Locations

CN(2)