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

Phase 1

• Conditions: HIV
• Interventions: Drug: Triptolide; Drug: cART; Drug: placebo

• Registration Number: NCT01817283
• Lead Sponsor: LI Taisheng

Brief Summary

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.

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.

Study Timeline

• Study Start: 2013-01
• Status Verified: 2013-03
• Study First Submitted: 2013-03-18
• Study First Submitted QC: 2013-03-22
• Last Update Submitted: 2013-03-22
• Study First Posted: 2013-03-25
• Last Update Posted: 2013-03-25
• Primary Completion: 2014-07
• Study Completion: 2015-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 150

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
placebo + cART	Triptolide	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
placebo + cART	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
placebo + cART	placebo	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
Triptolide + cART	cART	combined antiretroviral therapy, the experimental group will take Triptolide 2 tabs tid po per day for 12 months.
Triptolide + cART	Triptolide	combined antiretroviral therapy, the experimental group will take Triptolide 2 tabs tid po per day for 12 months.

Primary Outcome Measures

Name	Time	Method
Changes of T cell immune activation and inflammation biomarkers	baseline and at 4,8,12,24,36,48 weeks	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

Name	Time	Method
Changes of CD4 T cell count and number of participants with adverse events	baseline and at 4,8,12,24,36,48 weeks	Measurement of CD4 T cell count at baseline and different visit points when follow-up and numbers of participants with adverse events.

Trial Locations

Locations (1)

Peking Union Medical College Hospital; 🇨🇳 Beijing, China