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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01944371




Registration number
NCT01944371
Ethics application status
Date submitted
12/09/2013
Date registered
17/09/2013
Date last updated
5/05/2020

Titles & IDs
Public title
Short-term Disulfiram Administration to Reverse Latent HIV Infection: a Dose Escalation Study
Scientific title
Short-term Disulfiram Administration to Reverse Latent HIV Infection: a Dose Escalation Study
Secondary ID [1] 0 0
DAIDS-ES ID 11864
Secondary ID [2] 0 0
13-10948
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV 0 0
Human Immunodeficiency Virus 0 0
Condition category
Condition code
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Disulfiram

Experimental: disulfiram 500mg - 500mg disulfiram by mouth per day for 3 days

Experimental: disulfiram 1000mg - 1000mg disulfiram by mouth per day for 3 days

Experimental: disulfiram 2000mg - 2000mg disulfiram per mouth per day for 3 days


Treatment: Drugs: Disulfiram
This study will provide open label disulfiram. Subjects will take 1 dose of disulfiram per day for 3 days.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Cell-associated HIV RNA
Timepoint [1] 0 0
Baseline and 3 days
Secondary outcome [1] 0 0
Plasma HIV RNA
Timepoint [1] 0 0
Baseline and 3 days
Secondary outcome [2] 0 0
Proviral HIV DNA
Timepoint [2] 0 0
Baseline and 30 days

Eligibility
Key inclusion criteria
- HIV-1 infection

- Age 18 or older

- HIV plasma viral load <50 copies/ml for at least 3 years with at least one measurement
per year and most recent viral load within 3 months of screening.

- Receiving combination antiretroviral therapy (at least 3 agents); subjects must be on
a efavirenz-based or a ritonavir-based regimen

- Two CD4+ T cell counts greater than 350 cell/µl in the six months prior to screening

- Willing to abstain from any alcohol one day before, during the three day period in
which disulfiram will be administered and the two week period immediately after
disulfiram administration
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Current alcohol use disorder or hazardous alcohol use

- Current use of any drug formulation that contains alcohol or that might contain
alcohol, including the gelatin capsule and liquid formulations of ritonavir,
ritonavir/lopinavir, amprenavir and fosamprenavir.

- Current use of tipranavir or maraviroc.

- Current use of zidovudine, stavudine or didanosine (as disulfiram potentially has
potent irreversible inhibitory effects on mitochondrial metabolism and hence could
exacerbate the toxicity of these drugs).

- Concurrent use of rivaroxaban ( a CYP3A metabolized medication) as the cytochrome P450
inhibitory effects of disulfiram on rivaroxaban are unknown.

- Current use of warfarin

- Patients who are intending to modify antiretroviral therapy in the next 2 weeks for
any reason.

- Serious illness requiring hospitalization or parental antibiotics within preceding 3
months

- A screening hemoglobin below 12.5 g/dL

- A screening TSH consistent with Hypothyroidism

- Significant renal disease or acute nephritis

- Significant myocardial disease or diagnosed coronary artery disease

- Significant respiratory disease

- History of psychosis, seizure disorder, abnormal electroencephalogram or brain damage
with significant persisting neurological deficit.

- Clinically active hepatitis as evidenced by clinical jaundice or Grade 2 or higher
liver function test abnormalities.

- Hepatic cirrhosis or decompensated chronic liver disease.

- Diabetes or current hypothyroidism.

- Concurrent treatment with immunomodulatory drugs, or exposure to any immunomodulatory
drug in past 16 weeks.

- Recent exposure (within the preceding 8 weeks) to any vaccine.

- Pregnant or breastfeeding women. Women of childbearing potential must have a negative
serum pregnancy test at screening and agree to use a double-barrier method of
contraception throughout the study period.

- Significant substance use, which in the opinion of the investigator, is likely to
interfere with the conduct of the study.

- Prior or current use of disulfiram, vorinostat or other experimental agent used with
the intent to perturb the HIV-1 viral reservoir

- Current use of an antiretroviral regimen which does not include either efavirenz or a
protease inhibitor

Study design
Purpose of the study
Basic Science
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/05/2014
Sample size
Target
Accrual to date
Final
30
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California

Funding & Sponsors
Primary sponsor type
Other
Name
University of California, San Francisco
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Monash University
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
amfAR, The Foundation for AIDS Research
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Government body
Name [3] 0 0
National Institute of Allergy and Infectious Diseases (NIAID)
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to determine the safety, pharmacology and bioactivity of
disulfiram in antiretroviral treated HIV-infected adults. The investigators primary
hypothesis is that 3 days of disulfiram will result in an increase in HIV transcription in
CD4+ T-cells in patients on suppressive antiretroviral therapy (ART).
Trial website
https://clinicaltrials.gov/ct2/show/NCT01944371
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Steven Deeks, MD
Address 0 0
University of Californa, San Francisco
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01944371