Immunologic Response to Kansui in Treated HIV+ Individuals: a Dose Escalation Study

NCT02531295 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: University of Utah #00100155
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the safety and bioactivity of an herbal supplement called "kansui," which contains several active ingredients such as ingenols that may have a role in helping clear HIV from the body. Kansui has been used in traditional Chinese medicine for centuries to treat various ailments such as for eliminating excess fluid in the abdomen or lungs, loosening phlegm from the chest, and relieving constipation. Based on preliminary in vitro data from our group, kansui extract powder is a potent activator of HIV transpcription in latently infected Jurkat cells. The investigators' hypothesis is that kansui extract powder prepared as tea will be safe and well-tolerated, elicit an in vivo immunologic response, and at the doses administered, increase HIV transcription in latently-infected cells among HIV-infected patients on suppressive antiretroviral therapy.

Conditions

HIV; Human Immunodeficiency Virus

Outcome Measures

Primary Outcomes (1)

• Safety of Euphorbia Kansui Extract Powder Prepared as Tea Assessed by the Number of Grade 2 or Higher Severity Adverse Events or Drug-related Laboratory Abnormalities That Exceed a Frequency of 5%

  The number of grade 2 or higher severity adverse events (AEs) or drug-related laboratory abnormalities that exceed a frequency of 5% over a 31 day study period.

  31 days

Secondary Outcomes (4)

• Early T Cell Immune Activation (Change in Percent CD69+ CD4+ and CD8+ T Cells From Baseline to 9 Days)

  Baseline and 9 days

• T Cell Immune Activation (Change in Percent CD38+HLA-DR+ CD4+ and CD8+ T Cells From Baseline to 9 Days)

  Baseline and 9 days

• HIV Reservoir Size (Change in HIV RNA Pol Levels in Copies/ug From Baseline to 9 Days)

  Baseline and 9 days

• HIV Reservoir Size (Plasma HIV RNA Level From Baseline to 9 Days)

  Baseline and 9 days

Study Arms (3)

Kansui 1g per day x 1 day

EXPERIMENTAL

Study participants will be given 1 g of Euphorbia kansui extract powder prepared as tea for a total of 1 daily dose.

Drug: Euphorbia kansui extract powder prepared as tea

Kansui 1g per day x 2 days

EXPERIMENTAL

Study participants will be given 1 g of Euphorbia kansui extract powder prepared as tea for a total of 2 consecutive daily doses.

Drug: Euphorbia kansui extract powder prepared as tea

Kansui 1g per day x 3 days

EXPERIMENTAL

Study participants will be given 1 g of Euphorbia kansui extract powder prepared as tea for a total of 3 consecutive daily doses.

Drug: Euphorbia kansui extract powder prepared as tea

Interventions

Euphorbia kansui extract powder prepared as tea DRUG

1 g of Euphorbia kansui extract powder, measured and reconstituted in 4 fluid ounces of boiled water allowed to cool and administered as tea, taken by mouth daily

Also known as: Kansui

Kansui 1g per day x 1 day; Kansui 1g per day x 2 days; Kansui 1g per day x 3 days

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed HIV-1 infection in adults aged 18 years or older.
• Continuous therapy with a DHHS recommended/alternative combination ART for least 36 months (at least 3 agents) at study entry with no regimen changes in the preceding 24 weeks.
• Maintenance of undetectable plasma HIV-1 RNA (\<40 copies/ml) for at least 36 months. Episodes of single HIV plasma RNA 50-500 copies.ml will not exclude participation if subsequent HIV plasma RNA is \<40 copies/ml.
• Two CD4+ T cell counts \>350 cells/μl in the six months prior to screening.

You may not qualify if:

• Pre-ART viral load \<2000 copies/ml (HIV controllers)
• Based on prior history and/or virologic testing, no alternative ART regimens are available in the event that the current ART regimen is compromised as a result of this study.
• Recent hospitalization in the last 90 days.
• Recent infection in the last 90 days requiring systemic antibiotics.
• Recent vaccination within the last 8 weeks prior to study scree or any study blood draw.
• Any known history of liver-related diseases including but not limited to: hepatic cirrhosis of decompensated chronic liver diseases; clinically active hepatitis B or C infection as evidenced by clinical jaundice or Grade 2 or higher liver function test abnormalities; any hepatic impairment, regardless of the graded liver function test abnormalities.
• Any known history of gastrointestinal diseases including but not limited to: history of diarrheal illness requiring the use of anti-motility agents including inflammatory bowel disease, chronic diarrhea not otherwise specified; history of gastrointestinal bleeding with hemoglobin below 12.5 g/dL; history of gastric or duodenal ulcers; inflammatory gastrointestinal disease such as Crohn's disease or ulcerative colitis
• Any renal disease (eGFR \< 90 ml/min) or acute nephritis.
• Screening hemoglobin below 12.5 g/dL.
• Screening TSH consistent with hypothyroidism.
• Significant myocardial disease (current myocarditis or reduced left ventricular ejection fraction below the lower limit of normal) or diagnosed coronary artery disease.
• Significant respiratory disease requiring oxygen.
• Diabetes or current hypothyroidism.
• Participants of reproductive potential or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test at screening. All participants of childbearing potential must agree to use a double-barrier method of contraception throughout the study period and up to 90 days after the last dose of kansui.
• Exposure to any immunomodulatory drug (including maraviroc) in the16 weeks prior to study.

Sponsors & Collaborators

• University of California, San Francisco: lead
• University of Utah: collaborator
• amfAR, The Foundation for AIDS Research: collaborator

Study Sites (1)

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Related Publications (3)

• Cary DC, Fujinaga K, Peterlin BM. Euphorbia Kansui Reactivates Latent HIV. PLoS One. 2016 Dec 15;11(12):e0168027. doi: 10.1371/journal.pone.0168027. eCollection 2016.

  PMID: 27977742 RESULT

• Wang P, Lu P, Qu X, Shen Y, Zeng H, Zhu X, Zhu Y, Li X, Wu H, Xu J, Lu H, Ma Z, Zhu H. Reactivation of HIV-1 from Latency by an Ingenol Derivative from Euphorbia Kansui. Sci Rep. 2017 Aug 25;7(1):9451. doi: 10.1038/s41598-017-07157-0.

  PMID: 28842560 RESULT

• Liu Q, Li W, Huang L, Asada Y, Morris-Natschke SL, Chen CH, Lee KH, Koike K. Identification, structural modification, and dichotomous effects on human immunodeficiency virus type 1 (HIV-1) replication of ingenane esters from Euphorbia kansui. Eur J Med Chem. 2018 Aug 5;156:618-627. doi: 10.1016/j.ejmech.2018.07.020. Epub 2018 Jul 19.

  PMID: 30031972 RESULT

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Tea

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Plant Preparations; Biological Products; Complex Mixtures; Beverages; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Results Point of Contact

• Title: Sulggi Lee, MD PhD
• Organization: University of California, San Francisco

sulggi.lee@ucsf.edu

415-735-5127

Study Officials

• Sulggi A Lee, MD PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Adam M Spivak, MD

  University of Utah

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 20, 2015
• First Posted: August 24, 2015
• Study Start: May 15, 2019
• Primary Completion: March 19, 2020
• Study Completion: March 19, 2020
• Last Updated: April 19, 2024
• Results First Posted: April 19, 2024

Record last verified: 2024-04

Locations

US (1)