Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Euphorbia Kansui and HIV/AIDS Functional Cure

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04503928
Recruitment Status : Not yet recruiting
First Posted : August 7, 2020
Last Update Posted : August 10, 2020
Sponsor:
Collaborators:
Fudan University
Shanghai Xinhao Biological Technology Co., Ltd.
Information provided by (Responsible Party):
Hongzhou Lu, Shanghai Public Health Clinical Center

Brief Summary:
The purpose of this study is to determine the safety and bioactivity of Euphorbia kansui, which has been used in traditional Chinese medicine for the treatment of edema, ascites, and asthma. The investigators previously reported that effective fractions from the dichloromethane extracts of the roots of Euphorbia kansui can reactivate latent HIV-1 replication in different latent cells (The 24th China science technology Forum-High level Forum on HIV cure, December 16-17, 2012, Beijing). Importantly, in resting CD4+ T cells of HIV-1-infected patients on suppressive antiretroviral therapy (ART), it could effectively induce ex vivo latent HIV-1 expression. Sera from rats receiving orally administered effective fractions were able to reactivate latent HIV-1. The investigators also found a substantially potent ingenol derivative EK-16A, EK-1A, EK-5A, EK-15A from Euphorbia kansui and proved that it was potent in reversing HIV-1 latency. The investigators' hypothesis is that Euphorbia kansui Pill will be safe and well-tolerated and at the doses administered, increase HIV transcription in latently-infected cells among HIV-infected patients on suppressive antiretroviral therapy.

Condition or disease Intervention/treatment Phase
HIV-1-infection Drug: Euphorbia kansui Pill Phase 1

Detailed Description:

Every participant will receive oral Euphorbia kansui Pill every day. The dose of Euphorbia kansui will be 1g each time for 7 consecutive days. All participants will keep their antiretroviral therapy during this study.

Each step of this study will last for 21 days, involving 7 study visits (Screening,Day 0, 1, 3, 5, 7, 14, 21) for every participant. At the screening visit, participants will give a medical history and will undergo a physical exam; blood samples will be collected. Participants will undergo pharmacodynamic sampling which will require that blood be collected 12 hours after kansui Pill administration on Day 1, 3, 5,7. If participants agree, their blood samples may be stored for future research.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: All participants eligible for study received the same open label drug
Masking: None (Open Label)
Masking Description: Open label
Primary Purpose: Treatment
Official Title: Euphorbia Kansui in Combination With Antiretroviral Therapy for Eradication of the Latent HIV-1 Reservoir
Estimated Study Start Date : August 2020
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Experimental: Kansui 1g per day x 7 days
Study participants will be given 1 g of Euphorbia kansui Pill for a total of 7 consecutive daily doses.
Drug: Euphorbia kansui Pill
1 g (10 pills) of Euphorbia kansui Pill taken by mouth, once a day for 7 consecutive days.
Other Name: kansui




Primary Outcome Measures :
  1. Change in plasma HIV-1 RNA concentration [ Time Frame: Measured on day 0; 1, 3, 5, 7 (12 hours post administration); 14, 21. ]
  2. Change in cell-associated HIV-1 RNA [ Time Frame: on day 0; 1, 3, 5, 7 (12 hours post administration); 14, 21 ]
  3. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: Measured through 21 days after the first administration of kansui Pill ]

Secondary Outcome Measures :
  1. Change in cell-associated total HIV-1 DNA [ Time Frame: Measured on day 0, 14, 21 ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. HIV-1 infection
  2. Age ≥18 years; Willingness to give written informed consent.
  3. Karnofsky performance status >70.
  4. Able, willing to adhere to therapy and adherent to ART.
  5. Able, willing to comply with time requirements for study visits and evaluations.
  6. On potent combination ART for ≥ 18 months prior to study entry.
  7. Able to swallow pills without difficulty.
  8. HIV-1 RNA values <50 copies/mL for at least 18 months.
  9. CD4 cell count ≥ 500 cells/µl at screening.
  10. CD4 T cells isolated in vitro and stimulated with kansui, and the kansui activation test is positive.
  11. All volunteers must agree not to participate in a conception process.
  12. Must have adequate organ function as indicated by the following lab values:

Hematological: Absolute Neutrophil Count (ANC) ≥ 1,500/mcL Platelets ≥ 125,000/mcL Hgb ≥ 12 g/dL Coagulation: Prothrombin Time or International Normalized Ratio (INR) ≤ 1.5x upper limit of normal (ULN) Chemistry: K+ levels Within normal limits Mg++ levels > Lower limits of normal (LLN) but <1.5 x ULN Glucose Screening serum glucose(fasting/non-fasting) below 120 mg/dl.

Renal: Serum creatinine/calculated creatinine clearance* ≤ 1.3 X ULN OR ≥ 60 mL/min for participants with creatinine levels > 1.3 X ULN Hepatic: Serum total bilirubin Total bilirubin < 1.5 times ULN. If total bilirubin is elevated, direct bilirubin will be measured and the participant will be eligible if the direct bilirubin is < 2 X ULN.

Aspartate amino transferase (AST) (SGOT) and Alanine amino transferase (ALT) (SGPT)≤ 2.0 X ULN Lipase <1.6 X ULN Alkaline Phosphatase ≤ 2.5 X ULN.

Exclusion Criteria:

  1. Acute HIV-1 infection
  2. Received blood transfusions or hematopoetic growth factors within 3 months
  3. Receipt of compounds with other latency activators within 1 month.
  4. Any significant acute medical illness in the past 8 weeks
  5. Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood
  6. Patient has the following laboratory values within 3 weeks before starting the investigational drug Hepatic transaminases (AST or ALT) ≥3 x upper limit of normal (ULN) Serum total bilirubin ≥1.5 ULN Serum creatinine levels ≥1.5 x ULN, or calculated creatinine clearance ≤60 ml/min Platelet count ≤100 x109/L Absolute neutrophil count ≤1.5x109/L Serum potassium, magnesium, phosphorus outside normal limits Total calcium (corrected for serum albumin) or ionized calcium ≤lower normal limits
  7. A personal history of clinically significant cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or additional risk factors for Torsades de pointes (e.g. heart failure)
  8. History of malignancy or transplantation, including skin cancers or Kaposi sarcoma
  9. History of diabetes mellitus
  10. Known hypersensitivity to Kansui
  11. Pregnancy or breast feeding, or expecting to father children within the projected duration of the study
  12. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04503928


Contacts
Layout table for location contacts
Contact: Huanzhang Zhu, M.D. 31246728 hzzhu@fudan.edu.cn
Contact: Jingna Xun, MD 37990333 ext 5321 xunjingna@shphc.org.cn

Locations
Layout table for location information
China
Shanghai,China, Fudan University
Shanghai, China
Contact: Huanzhang Zhu, M.D.         
Principal Investigator: Huanzhang Zhu, M.D.         
Principal Investigator: Hongzhou Lu, M.D.         
Sponsors and Collaborators
Shanghai Public Health Clinical Center
Fudan University
Shanghai Xinhao Biological Technology Co., Ltd.
Investigators
Layout table for investigator information
Principal Investigator: Hongzhou Lu, M.D. Shanghai Public Health Clinical Center
Principal Investigator: Huanzhang Zhu, M.D. Fudan University
Additional Information:
Publications:
Layout table for additonal information
Responsible Party: Hongzhou Lu, professor, Shanghai Public Health Clinical Center
ClinicalTrials.gov Identifier: NCT04503928    
Other Study ID Numbers: Euphorbia kansui V1
First Posted: August 7, 2020    Key Record Dates
Last Update Posted: August 10, 2020
Last Verified: August 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No