Impact on T Cell Immune Activation and Inflammation of Triptolide Woldifii in HIV-infected Immunological Non-responders (CACTrip12)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2013 by Peking Union Medical College
Sponsor:
Information provided by (Responsible Party):
LI Taisheng, Peking Union Medical College
ClinicalTrials.gov Identifier:
NCT01817283
First received: March 18, 2013
Last updated: March 22, 2013
Last verified: March 2013
  Purpose

This study is a prospective, multicenter, randomized, placebo-controlled clinical trial, to evaluate impact of Triptolide wilfordii on T cell immune activation and inflammation biomarkers in HIV-infected immunological non-responders.


Condition Intervention Phase
HIV
Drug: Triptolide
Drug: cART
Drug: placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Study of Triptolide Woldifiion T Cell Immune Activation and Inflammation Biomarkers in HIV-infected Immunological Non-responders

Resource links provided by NLM:


Further study details as provided by Peking Union Medical College:

Primary Outcome Measures:
  • Changes of T cell immune activation and inflammation biomarkers [ Time Frame: baseline and at 4,8,12,24,36,48 weeks ] [ Designated as safety issue: No ]
    T cell activation and inflammatory biomarkers including CD8+HLA-DR+/CD38+, IL-6, D-dimer and hsCRP,soluble CD14 and CD163, PD-1, CCR5 and CD57 should be measured at baseline and at Wee4, W12, W24, W36, W48 follow-up visits.


Secondary Outcome Measures:
  • Changes of CD4 T cell count and number of participants with adverse events [ Time Frame: baseline and at 4,8,12,24,36,48 weeks ] [ Designated as safety issue: Yes ]
    Measurement of CD4 T cell count at baseline and different visit points when follow-up and numbers of participants with adverse events.


Estimated Enrollment: 150
Study Start Date: January 2013
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: placebo + cART
combined with antiretroviral therapy, the control group will take placebo 2 tabs tid per day lasting for 6 months and then switch to take Triplitode 2 tabs tid po for anther 6 months
Drug: Triptolide
Triptolide Wilfordii is a Chinese old herb which is widely used as a remedy for rheumatic diseases and nephropathy in China. It is approved that it can play a role as an immune modular.
Other Name: Tripterygium Wilfordii Hook F (TwHF)
Drug: cART
Participants who will be enrolled in this trial would keep their previous combined antiretroviral therapy, such as zidovudine or stavudine plus lamivudine plus nevirapine or efavirenz.
Other Name: Antiretroviral therapy
Drug: placebo
Placebo pills produced the same as Triptolide wilfordii.
Other Name: sugar pills
Experimental: Triptolide + cART
combined antiretroviral therapy, the experimental group will take Triptolide 2 tabs tid po per day for 12 months.
Drug: Triptolide
Triptolide Wilfordii is a Chinese old herb which is widely used as a remedy for rheumatic diseases and nephropathy in China. It is approved that it can play a role as an immune modular.
Other Name: Tripterygium Wilfordii Hook F (TwHF)
Drug: cART
Participants who will be enrolled in this trial would keep their previous combined antiretroviral therapy, such as zidovudine or stavudine plus lamivudine plus nevirapine or efavirenz.
Other Name: Antiretroviral therapy

Detailed Description:

About 120 patients will be recruited from 4 HIV/AIDS clinical centers in China and randomized 1:1 into intervention group and placebo-controlled group. Triptolide wilfordii (20mg tid po) would be given to invention group for 24 weeks. T cell activation and inflammation biomarkers including CD8+HLA-DR+CD38+, IL-6, D-Dimer and high-sensitivity C-reactive protein (hsCRP), protein degradation-1 (PD-1), Ki67 ,soluble CD14 and CD163, PD-1, CCR5 and CD57 would be tested. Patients in placebo-controlled group will change to take Triptolide wilfordii (20mg tid po) for another 24 weeks. All patients will be followed up till 48 weeks. We hypothesis that Triptolide wilfordii might reduce immune activation and inflammation of HIV immunological non-responders and increase CD4 T cell count, which provides a new strategy for treatment of HIV-infected immunological non-responders.

  Eligibility

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

Inclusion Criteria:

  • Continuous antiretroviral therapy > 24 months , and consistent HIV-RNA< 40 copies/mL more than 12 months ;
  • 18-65 years old;
  • Male or female;
  • Good adherence and promise to follow-up;
  • Inform Consent signed;
  • CD4 T cells less than 250/ul .

Exclusion Criteria:

  • Active opportunistic infection (not stable within 4 weeks 2 weeks ) or AIDS-related carcinoma;
  • hemoglobin (HGB) < 9 g/dl 、 white blood cell (WBC) < 2000/ul 、 granulin (GRN) < 1000 /ul 、 platelet (PLT) < 75000 /ul 、 Cr >1.5x ULN 、 ALT or AST or alkaline phosphatase (ALP) >3x upper limit of normal (ULN) 、 total bilirubin (TBIL) >2x ULN 、 creatine kinase (CK) > 2x ULN;
  • Pregnant or breastfeeding woman or woman with pregnancy plan;
  • Active drug-user;
  • Severe neurological defects;
  • Active alcohol abuse;
  • Severe gastrointestinal ulcer .
  • End-stage disease such as cirrhosis, chronic obstructive pulmonary disease, congestive heart failure, recent myocardial ischemia,tumor, etc
  • Those who are undertaking steroids, immunomodulator, anti-inflammatory agents
  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: NCT01817283

Contacts
Contact: Wei LU, M.D. 00861069155081 lvweipumch@163.com

Locations
China
Peking Union Medical College Hospital Recruiting
Beijing, China, 100730
Contact: Wei LU, M.D.    00861069155081    lvweipumch@163.com   
Sponsors and Collaborators
LI Taisheng
Investigators
Principal Investigator: Tai sheng LI, M.D. Peking Union Medical College Hospital
  More Information

No publications provided

Responsible Party: LI Taisheng, Peking Union Medical College Hospital, Peking Union Medical College
ClinicalTrials.gov Identifier: NCT01817283     History of Changes
Other Study ID Numbers: CACTRIP12
Study First Received: March 18, 2013
Last Updated: March 22, 2013
Health Authority: China: Food and Drug Administration

Keywords provided by Peking Union Medical College:
HIV-infected immunological non-responders
Triptolide
immune activation
inflammation
CD4 T cell

Additional relevant MeSH terms:
Inflammation
Pathologic Processes
Triptolide
Antispermatogenic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Contraceptive Agents, Male
Contraceptive Agents
Reproductive Control Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on October 19, 2014