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Therapy to Elevate CD4 Counts in HIV-1 Disease

Primary Purpose

HIV Disease

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

alpha-1-Proteinase Inhibitor

About this trial

This is an interventional treatment trial for HIV Disease focused on measuring CD4 counts, cholesterol

Eligibility Criteria

30 Years - 70 Years (Adult, Older Adult)MaleAccepts Healthy Volunteers

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.

Sites / Locations

Cabrini Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

alpha-1 proteinase inhibitor in HIV

Arm Description

HIV-1 infected individuals treated with Alpha-1 proteinase inhibitor

Outcomes

Primary Outcome Measures

CD4/CD8 Ratio

Secondary Outcome Measures

Full Information

NCT ID

NCT01370018

First Posted

June 6, 2011

Last Updated

August 31, 2021

Sponsor

Institute for Human Genetics and Biochemistry

Collaborators

CSL Behring

1. Study Identification

Unique Protocol Identification Number

NCT01370018

Brief Title

Therapy to Elevate CD4 Counts in HIV-1 Disease

Official Title

Zemaira (Alpha-1-Proteinase Inhibitor) Therapy in HIV-1 Disease

Study Type

Interventional

2. Study Status

Record Verification Date

August 2021

Overall Recruitment Status

Completed

Study Start Date

December 2006 (undefined)

Primary Completion Date

February 2007 (Actual)

Study Completion Date

February 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Institute for Human Genetics and Biochemistry

Collaborators

CSL Behring

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief Summary

For more than 20 years, alpha-1-proteinase inhibitor therapy has been the standard treatment for patients who have inherited alpha-1-proteinase inhibitor deficiency. Adult patients with this condition eventually develop emphysema. Most HIV-1 patients who have low viral load also have alpha-1-proteinase inhibitor deficiency. The number of CD4 cells in blood increases when alpha-1-proteinase inhibitor increases. Patients will be asked to participate in a pilot study to see whether the use of Zemaira® (alpha-1-proteinase inhibitor) can increase blood levels of alpha-1-proteinase inhibitor and consequently increase CD4 counts.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV Disease

Keywords

CD4 counts, cholesterol

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

4 (Actual)

8. Arms, Groups, and Interventions

Arm Title

alpha-1 proteinase inhibitor in HIV

Arm Type

Experimental

Arm Description

HIV-1 infected individuals treated with Alpha-1 proteinase inhibitor

Intervention Type

Biological

Intervention Name(s)

alpha-1-Proteinase Inhibitor

Other Intervention Name(s)

Zemaira, Prolastin

Intervention Description

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.

Primary Outcome Measure Information:

Title

CD4/CD8 Ratio

Time Frame

9 weeks after initiation of treatment

10. Eligibility

Sex

Male

Gender Based

Yes

Gender Eligibility Description

Female subjects were not included in this pilot study to avoid pregnancy-related issues.

Minimum Age & Unit of Time

30 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Cynthia L Bristow, PhD

Organizational Affiliation

Icahn School of Medicine at Mount Sinai

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Jose Cortes, MD

Organizational Affiliation

Beth Israel Medical Center

Official's Role

Study Director

Facility Information:

Facility Name

Cabrini Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10003

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

Citation

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

Results Reference

result

PubMed Identifier

24229737

Citation

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.

Results Reference

result

PubMed Identifier

31824943

Citation

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.

Results Reference

result

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Therapy to Elevate CD4 Counts in HIV-1 Disease

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