- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01370018
Therapy to Elevate CD4 Counts in HIV-1 Disease
Zemaira (Alpha-1-Proteinase Inhibitor) Therapy in HIV-1 Disease
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
HIV-1 patients will be asked to participate in a pilot study to see whether the use of Zemaira increases blood levels of alpha-1-proteinase inhibitor and consequently increase CD4 counts.
HIV-1 patients will receive weekly treatment with Zemaira for 8 weeks by intravenous infusion. Blood will be collected immediately prior to each infusion. Blood will be collected at each visit. Exploratory assessments and not pre-specified outcome measurements will include complete blood count, lymphocyte phenotype, HIV-1 viral load, lipid levels, blood chemistry, and markers of inflammation from patient medical records. Exploratory and not pre-specified outcome measures will include extended lymphocyte phenotype and lymphocyte function using residual blood collected.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Locations
-
-
New York
-
New York, New York, United States, 10003
- Cabrini Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- HIV-1 patients must have confirmed HIV-1 disease, diagnosed using the standard criteria and be on antiretroviral therapy. Patients with inherited alpha-1 proteinase inhibitor deficiency (PIzz) must not have previously received alpha-1 proteinase inhibitor therapy. Uninfected volunteers will be age and gender matched.
- HIV-1 patients must have measurable disease, defined as HIV-1 infected patients on antiretroviral therapy with undetectable HIV RNA (<500 HIV-1 RNA copies/ml) and CD4 counts more than 200 and less than 400 cells/uL.
- Age at least 18 years and under 65 years.
- HIV-1 patients must have active alpha-1 proteinase inhibitor below 11uM (normal is 18-53 uM).
- HIV-1 patients must have one year history (prior to the study) with CD4 counts greater than 200 and less than 400 cells/uL.
- Volunteers must have no evidence of malignancy.
Exclusion Criteria:
- Recent illness that will prevent the patient from participating in required study activities.
- Patients receiving other investigational agents.
- Patients with known malignancies.
- Patients with more than 500 HIV RNA copies/mL.
- Patients with more than 400 CD4 cells/uL.
- Uncontrolled illness including, but not limited to, ongoing or active infection, myeloid dysplastic syndrome, anemia, bone marrow failure, DiGeorge Syndrome, thymic disorders, or psychiatric illness/social situations that would limit compliance with study requirements.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: alpha-1 proteinase inhibitor in HIV
HIV-1 infected individuals treated with Alpha-1 proteinase inhibitor
|
Alpha-1-Proteinase Inhibitor was delivered I.V.
A patient weighing 150 pounds was infused with approximately ½ cup containing 8.4 grams of alpha-1-Proteinase Inhibitor.
Patients were admitted to hospital for infusion.
The I.V. infusion was approximately 1 teaspoon/minute.
Patients received weekly infusions of alpha-1-Proteinase Inhibitor for 8-12 weeks.
At the time of infusion, 40ml (3 Tablespoons) of blood was collected (IRB approval #R04-003).
The blood sample was used to monitor viral load, CD4 cell numbers, and alpha-1-Proteinase Inhibitor.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
CD4/CD8 Ratio
Time Frame: 9 weeks after initiation of treatment
|
9 weeks after initiation of treatment
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Cynthia L Bristow, PhD, Icahn School of Medicine at Mount Sinai
- Study Director: Jose Cortes, MD, Beth Israel Medical Center
Publications and helpful links
General Publications
- Bristow CL, Ferrando-Martinez S, Ruiz-Mateos E, Leal M, Winston R. Development of Immature CD4+CD8+T Cells Into Mature CD4+ T Cells Requires Alpha-1 Antitrypsin as Observed by Treatment in HIV-1 Infected and Uninfected Controls. Front Cell Dev Biol. 2019 Nov 21;7:278. doi: 10.3389/fcell.2019.00278. eCollection 2019.
- Bristow, C.L., Cortes, J., Mukhtarzad R., Trucy, M., Franklin, A., Romberg, V., Winston, R. 2010. α1Antitrypsin therapy increases CD4+ lymphocytes to normal values in HIV-1 patients. In Soluble Factors Mediating Innate Immune Responses to HIV Infection, (ed. M. Alfano). Bentham Science Publishers, http://www.alpha1biologics.com/BristowChapter.pdf
- Bristow CL, Modarresi R, Babayeva MA, LaBrunda M, Mukhtarzad R, Trucy M, Franklin A, Reeves RE, Long A, Mullen MP, Cortes J, Winston R. A feedback regulatory pathway between LDL and alpha-1 proteinase inhibitor in chronic inflammation and infection. Discov Med. 2013 Nov;16(89):201-18.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- Slow Virus Diseases
- HIV Infections
- Acquired Immunodeficiency Syndrome
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Serine Proteinase Inhibitors
- Trypsin Inhibitors
- Protease Inhibitors
- Alpha 1-Antitrypsin
Other Study ID Numbers
- R06-005
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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