Safety and Efficacy of Triptolide Wilfordii in New Onset HIV-1 Infection

Impact of Triptolide Wilfordii on Viral Suppression, Immune Recovery and Immune Activation Biomarkers in Treatment-naive HIV-1 Infection: a Randomized, Double-blinded, Placebo-controlled Study

The traditional Chinese herbal medicine Triptolide Wilfordii has displayed remarkable effect on the treatment of autoimmune diseases such as rheumatoid arthritis. Now that immunosuppression therapy has recently become a new strategy for HIV infection, it's reasonable to expect the anti-inflammatory effect of Triptolide Wilfordii in HIV infected patients. So we designed a randomized, double-blinded, placebo-controlled study to explore the efficacy and safety of Triptolide Wilfordii in new-onset HIV infection.

Study Overview

• Status: Completed
• Conditions: HIV-infection/AIDS
• Intervention / Treatment: Drug: Triptolide Wilfordii; Drug: Placebo Oral Tablet

Detailed Description

Acquired immune deficiency syndrome(AIDS) is a severe fatal disease caused by HIV infection. Despite viral suppression achieved, antiretroviral therapy(ART) cannot ameliorate HIV-induced immune activation and the consequent non-AIDS complications including cardiovascular, renal, hepatic diseases. Recently, immunosuppression therapy has become the focus since it can suppress exorbitant immune activation and inflammation so as to reduce the risk of non-AIDS cardiovascular and central neural system complications. Triptolide Wilfordii is a traditional Chinese herbal remedy and has long been used in the treatment of autoimmune diseases such as rheumatoid arthritis. Moreover, a recent study has shown that Triptolide Wilfordii combined with ART is associated with increased CD4 T cell counts and reduced immune activation in immunological non-responders, who were defined as patients with CD4 cell counts<350 cells/μl despite over 2 years of ART. Hence we expect Triptolide Wilfordii to bring up similar improvement in treatment naïve HIV infection. This randomized, double-blinded, placebo-controlled study is designed to investigate the safety and efficacy of Triptolide Wilfordii and hopefully provide evidence for a new treatment strategy.

• Study Type: Interventional
• Enrollment (Actual): 353
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100069
    • Beijing Youan Hospital, Capital Medical University
  • Beijing, China, 100191
    • Beijing Ditan Hospital, Capital Medical University
  • Fujian
    • Fuzhou, Fujian, China, 350025
      • Mengchao Hepatobiliary Hospital of Fujian Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • The Eighth People's Hospital of Guangzhou
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150001
      • The Fourth Affiliated Hospital of Harbin Medical University
  • Henan
    • Zhengzhou, Henan, China, 450015
      • The Sixth People's Hospital of Zhengzhou
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310023
      • Xixi hospital of Hangzhou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18~65 years old;
• Male or female;
• Good adherence and promise to follow-up;
• Inform Consent signed;
• Positive for HIV antibody test or serum HIV-RNA positive for 2 times or more;

Exclusion Criteria:

• Present opportunity infection defined according to national AIDS treatment guideline or active opportunistic infection(not stable within 14 days ) within 3 months before recruitment or AIDS-related carcinoma;
• Hemoglobin (HGB) < 9 g/dl, white blood cell (WBC) < 3000/ul, granulin (GRN) < 1500 /ul, platelet (PLT) < 75000 /ul, Cr >1.5x upper limit of normal (ULN), ALT or AST or alkaline phosphatase (ALP) >3x ULN, total bilirubin (TBIL) >2x ULN;
• Pregnancy or breastfeeding;
• Woman with pregnancy plan;
• Severe organ dysfunction;
• Administration of immunosuppressor, immunomodulator(including thymocin) or systemic cytotoxic drugs within 6 months before recruitment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Triptolide Wilfordii Group; 150 patients will be enrolled and be administrated with Triptolide Wilfordii 20mg three times a day(TID) per os combined with appropriate ART for 12 months.	Drug: Triptolide Wilfordii; In addition to appropriate ART, Triptolide Wilfordii will be given to patients in the experimental group at a dosage of 20mg three times a day per os for 12 months.
Placebo Comparator: Placebo Oral Tablet Group; 150 patients will be enrolled and be administrated with placebo per os combined with appropriate ART for 12 months.	Drug: Placebo Oral Tablet; In addition to appropriate ART, placebo oral tablets will be given to patients in the experimental group at a dosage of 2 pills three times a day per os for 12 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CD4 T cell counts and HIV RNA	Compared to patients in placebo group, CD4 T cells of patients treated with Triptolide Wilfordii significantly increase and HIV RNA is reduced below 20 copies/ml.	Baseline, Week4, Week12, Week24, Week36, Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune activation	Compared to patients in placebo group, immune activation index of patients treated with Triptolide Wilfordii decreases.	Baseline, Week4, Week12, Week24, Week36, Week 48
Inflammation level	Compared to patients in placebo group, inflammation level of patients treated with Triptolide Wilfordii decreases.	Baseline, Week4, Week12, Week24, Week36, Week 48
HIV reservoir	Compared to patients in placebo group, HIV reservoir of patients treated with Triptolide Wilfordii is reduced.	Baseline, Week4, Week12, Week24, Week36, Week 48

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2018
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): June 30, 2021

Study Registration Dates

• First Submitted: January 11, 2018
• First Submitted That Met QC Criteria: January 17, 2018
• First Posted (Actual): January 18, 2018

Study Record Updates

• Last Update Posted (Actual): April 8, 2022
• Last Update Submitted That Met QC Criteria: March 31, 2022
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: immune activation; anti-inflammation; CD4 cell recovery
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; Slow Virus Diseases; HIV Infections; Infections; Communicable Diseases; Acquired Immunodeficiency Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Male; Antispermatogenic Agents; Triptolide
• Other Study ID Numbers: PekingUMCH record JS-985

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No