HIVPhase 1NCT02531295

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

A Phase 1 study testing Euphorbia kansui extract powder prepared as tea in people with HIV and Human Immunodeficiency Virus, run by University of California, San Francisco at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: HIV, Human Immunodeficiency Virus
What is being tested?: Euphorbia kansui extract powder prepared as tea
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 5 participants
Where: 1 siteUnited States
Study dates: 15 May 2019to 19 Mar 2020
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Show all 19Show fewer

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.
Prior or current use of experiment agents used with the intent to perturb the HIV-1 viral reservoir.
History of seizures, psychosis, abnormal electroencephalogram or brain damage with significant persisting neurological deficit
Positive test for tuberculosis by either skin test (PPD) or blood interferon-gamma release assay (QuantiFERON).
Significant substance use, which in the opinion of the investigator(s), is likely to interfere with the conduct of the study.

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Utah
Salt Lake City, Utah, 84132

Other trials in United States

About this study

Official title: Immunologic Response to Euphorbia Kansui Extract Powder Prepared as Tea in HIV-infected Antiretroviral Therapy (ART)-Suppressed Individuals: a Dose Escalation Study

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.

Read the detailed description

Millions HIV-infected individuals are now receiving life-saving antiretroviral therapy (ART). However, mortality remains high, particularly in resource-limited countries. Chronic HIV-infected individuals demonstrate evidence of persistent immune activation despite ART, which is an independent predictor of mortality in this setting. Given the current absence of an effective HIV vaccine, finding a cure for HIV will have a large impact on the long-term health of treated HIV-infected individuals. The key challenge of HIV eradication strategies is the persistence of a small pool of resting memory CD4+ T cells that harbor latent replication-competent HIV, untouched by current ART. One potential strategy to eliminate this reservoir in a "shock and kill" approach in which latency reactivating agents (LRAs) are used to "shock" the virus out of these cells in order for the host immune response, ART, and/or additional immunomodulatory agents to then kill the virus-expressing cells. The goal of the current study is to evaluate the safety and in vivo biological response to an herbal supplement used in traditional Chinese medicine ("kansui)" that has potent in vitro latency reactivating capabilities. Kansui is an inexpensive, readily available herbal supplement prescribed for thousands of years in traditional Chinese medicine and contains active compounds such as ingenols that have been shown to reverse latency in an animal model. A semi-synthetic form of ingenol has been shown to potently reactivate latent simian immunodeficiency virus (SIV) in rhesus macaques and is currently undergoing early drug development. Though kansui has been studied extensively in traditional Chinese medicine, this herbal supplement has never been evaluated for biologic activity in HIV disease using Western scientific research methods. This pilot clinical trial will generate preliminary results regarding the safety and in vivo biologic activity of kansui. Promising results from this study may allow future larger studies which can evaluate the efficacy of this non-pharmacologic agent in the treatment of HIV disease.

Conditions: HIV, Human Immunodeficiency Virus
Being tested: Euphorbia kansui extract powder prepared as tea
Medical subject headings: Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Euphorbia kansui extract powder prepared as teaDrug
Also called Kansui
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

Study groups in NCT02531295
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: Drug: Euphorbia kansui extract powder prepared as tea

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 31 days

Secondary outcomes (4)

Early T Cell Immune Activation (Change in Percent CD69+ CD4+ and CD8+ T Cells From Baseline to 9 Days)
The change in early immune activation levels (as measured by the Change in Percent CD69+ CD4+ and CD8+ T cells) over a 9 day study period.
Measured: Baseline and 9 days
T Cell Immune Activation (Change in Percent CD38+HLA-DR+ CD4+ and CD8+ T Cells From Baseline to 9 Days)
The change in immune activation levels (as measured by the percent change in CD38+HLADR+ CD4+ and CD8+ T cells) over a 9 day study period.
Measured: Baseline and 9 days
HIV Reservoir Size (Change in HIV RNA Pol Levels in Copies/ug From Baseline to 9 Days)
The change in HIV reservoir size (as measured by cell-associated unspliced ddPCR HIV RNA Pol levels in copies/ug) over a 9 day study period.
Measured: Baseline and 9 days
HIV Reservoir Size (Plasma HIV RNA Level From Baseline to 9 Days)
The change in HIV reservoir size (as measured by ultra-sensitive plasma HIV RNA levels) over a 9 day study period.
Measured: Baseline and 9 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 May 201919 Mar 2020

First posted24 Aug 2015 (estimated)
Study start15 May 2019
Primary completion19 Mar 2020
Study completion19 Mar 2020

Why it stopped: Pause on clinical trial enrollment due to grant funding cuts after COVID-19

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for HIVStudies of the same condition, open and under way.
More trials run by University of California, San FranciscoThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 5 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02531295
Sponsor's protocol ID: University of Utah #00100155
Status last verified: Apr 2024
First submitted: 20 Aug 2015
Last updated: 19 Apr 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

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.
PubMed 27977742
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.
PubMed 28842560
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.
PubMed 30031972

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 19 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Immunologic Response to Euphorbia Kansui Extract Powder Prepared as Tea in HIV-infected Antiretroviral Therapy (ART)-Suppressed Individuals: a Dose Escalation Study
ClinicalTrials.gov ID: NCT02531295
Acronym / sponsor ID: University of Utah #00100155
Conditions: HIV, Human Immunodeficiency Virus
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: Pause on clinical trial enrollment due to grant funding cuts after COVID-19
Enrolment: 5 participants (actual)
Lead sponsor: University of California, San FranciscoUniversity, hospital or other
Collaborators: University of Utah, amfAR, The Foundation for AIDS Research
Study start: 15 May 2019 (actual)
Primary completion: 19 Mar 2020 (actual)
Study completion: 19 Mar 2020 (actual)
First posted: 24 Aug 2015 (estimated)
Results: Posted 19 Apr 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Kansui 1g per day x 1 day	Experimental	Drug: Euphorbia kansui extract powder prepared as teaStudy participants will be given 1 g of Euphorbia kansui extract powder prepared as tea for a total of 1 daily dose.
Kansui 1g per day x 2 days	Experimental	Drug: Euphorbia kansui extract powder prepared as teaStudy participants will be given 1 g of Euphorbia kansui extract powder prepared as tea for a total of 2 consecutive daily doses.
Kansui 1g per day x 3 days	Experimental	Drug: Euphorbia kansui extract powder prepared as teaStudy participants will be given 1 g of Euphorbia kansui extract powder prepared as tea for a total of 3 consecutive daily doses.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (19 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Euphorbia kansui extract powder prepared as teaAlso: Kansui1 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	Drug	Kansui 1g per day x 1 day, Kansui 1g per day x 2 days, Kansui 1g per day x 3 days

Primary outcome

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%
Time frame: 31 days
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.

4 secondary outcomes

Early T Cell Immune Activation (Change in Percent CD69+ CD4+ and CD8+ T Cells From Baseline to 9 Days)
Time frame: Baseline and 9 days
T Cell Immune Activation (Change in Percent CD38+HLA-DR+ CD4+ and CD8+ T Cells From Baseline to 9 Days)
Time frame: Baseline and 9 days
HIV Reservoir Size (Change in HIV RNA Pol Levels in Copies/ug From Baseline to 9 Days)
Time frame: Baseline and 9 days
HIV Reservoir Size (Plasma HIV RNA Level From Baseline to 9 Days)
Time frame: Baseline and 9 days

Results and safety

Results posted to the registry on 19 Apr 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Kansui 1g Per Day x 1 Day	2	2
Kansui 1g Per Day x 2 Days	0	0
Kansui 1g Per Day x 3 Days	1	1
Placebo 1g Per Day x 1 Day	0	0
Placebo 1g Per Day x 2 Days	0	0
Placebo 1g Per Day x 3 Days	2	1

Primary outcome: 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%

Time frame: 31 days. Count of participants. Unit: Participants

Measure	Kansui 1g Per Day x 1 Day n = 2	Kansui 1g Per Day x 2 Days n = 0	Kansui 1g Per Day x 3 Days n = 1	Placebo 1g Per Day x 1 Day n = 0	Placebo 1g Per Day x 2 Days n = 0	Placebo 1g Per Day x 3 Days n = 2
Value	0	0	0	0	0	0

Population analysed: The study was terminated (Halted Prematurely).

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: The total duration of the study was approximately 10 months from May 15, 2019 to March 19, 2020. Each participant was assessed for 31 days during the duration of their enrollment in the study. No severe adverse events occurred during the trial. There were no discontinuations or participants who left the trial early.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Kansui 1g Per Day x 1 Day	0 of 2 (0%)	0 of 2 (0%)	0 of 2
Kansui 1g Per Day x 2 Days	0 of 0	0 of 0	0
Kansui 1g Per Day x 3 Days	0 of 1 (0%)	0 of 1 (0%)	0 of 1
Placebo 1g Per Day x 1 Day	0 of 0	0 of 0	0
Placebo 1g Per Day x 2 Days	0 of 0	0 of 0	0
Placebo 1g Per Day x 3 Days	0 of 2 (0%)	0 of 2 (0%)	0 of 2

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 27977742Cary 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.
Results publication: PubMed 28842560Wang 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.
Results publication: PubMed 30031972Liu 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Sulggi A Lee, MD PhD principal investigator

University of California, San Francisco

Adam M Spivak, MD principal investigator

University of Utah

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Euphorbia kansui extract powder prepared as tea in people with HIV and Human Immunodeficiency Virus, run by University of California, San Francisco at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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% (time frame: 31 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02531295, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2024.