Therapy to Elevate CD4 Counts in HIV-1 Disease

NCT ID: NCT01370018

Last Updated: 2021-09-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-12-31
• Study Completion Date: 2007-02-28

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.

Conditions

HIV Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

alpha-1 proteinase inhibitor in HIV

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

Group Type: EXPERIMENTAL

alpha-1-Proteinase Inhibitor

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: BIOLOGICAL

Other Intervention Names

Zemaira; Prolastin

Eligibility Criteria

Inclusion Criteria

1. 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.

2. 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.

3. Age at least 18 years and under 65 years.

4. HIV-1 patients must have active alpha-1 proteinase inhibitor below 11uM (normal is 18-53 uM).

5. HIV-1 patients must have one year history (prior to the study) with CD4 counts greater than 200 and less than 400 cells/uL.

6. Volunteers must have no evidence of malignancy.

Exclusion Criteria

1. Recent illness that will prevent the patient from participating in required study activities.

2. Patients receiving other investigational agents.

3. Patients with known malignancies.

4. Patients with more than 500 HIV RNA copies/mL.

5. Patients with more than 400 CD4 cells/uL.

6. 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.

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

CSL Behring

INDUSTRY

Sponsor Role: collaborator

Institute for Human Genetics and Biochemistry

OTHER

Sponsor Role: lead

Responsible Party

Cynthia L Bristow, PhD

Assistant Professor, Mount Sinai School of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Cynthia L Bristow, PhD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Jose Cortes, MD

Role: STUDY_DIRECTOR

Beth Israel Medical Center

Locations

Cabrini Medical Center

New York, New York, United States

Countries

United States

References

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

Reference Type: RESULT

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.

Reference Type: RESULT

PMID: 24229737 (View on PubMed)

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.

Reference Type: RESULT

PMID: 31824943 (View on PubMed)

Other Identifiers

R06-005

Identifier Type: -

Identifier Source: org_study_id