Therapy to Elevate CD4 Counts in HIV-1 Disease

This study has been completed.
Sponsor:
Collaborator:
CSL Behring
Information provided by:
Cabrini Medical Centre
ClinicalTrials.gov Identifier:
NCT01370018
First received: June 6, 2011
Last updated: June 8, 2011
Last verified: December 2006
  Purpose

For more than 20 years, alpha-1-Proteinase Inhibitor therapy (Zemaira®) has been the standard treatment for patients who have too little alpha-1-Proteinase Inhibitor in blood. Adult patients with this condition eventually develop emphysema. Most HIV-1 patients who have low viral load also have too little alpha-1-Proteinase Inhibitor in blood. Recent strong evidence shows that the number of CD4 cells in blood goes up when alpha-1-Proteinase Inhibitor goes up. Patients were asked to participate in a pilot study to see whether the use of Zemaira® (alpha-1-Proteinase Inhibitor) would increase blood levels of alpha-1-Proteinase Inhibitor and consequently increase CD4 cells.


Condition Intervention
HIV Disease
Biological: alpha-1-Proteinase Inhibitor

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Zemaira (Alpha-1-Proteinase Inhibitor) Therapy in HIV-1 Disease

Resource links provided by NLM:


Further study details as provided by Cabrini Medical Centre:

Primary Outcome Measures:
  • Lymphocyte Phenotype [ Time Frame: 9 or 13 weeks. ] [ Designated as safety issue: Yes ]
    CD3, CD4, and CD8 cells/ul were assessed at the same time of day on the same day of the week each week for the duration of the study


Secondary Outcome Measures:
  • HIV-1 viral load [ Time Frame: 9 or 13 weeks. ] [ Designated as safety issue: Yes ]
    HIV -1 RNA copies/ml were assessed at the same time of day on the same day of the week each week for the duration of the study

  • Lipid levels [ Time Frame: 9 or 13 weeks. ] [ Designated as safety issue: Yes ]
    Total cholesterol, HDL, LDL, and triglycerides (mg/dL) were assessed at the same time of day on the same day of the week each week for the duration of the study

  • Blood Chemistry [ Time Frame: Multiple blood chemistry measures as listed in the Description were assessed once during the study between the 6th and 8th week. ] [ Designated as safety issue: Yes ]
    Total protein (gm/dL), Albumin (gm/dL), and Globulin (gm/dL), Glucose (mg/dL), Sodium (mmol/dL), Potassium (mmol/dL), Chloride (mmol/dL), CO2 (mmol/dL), BUN (mg/dL), Creatinine (mg/dL), Calcium (mg/dL), Uric acid (mg/dL), Iron (mcg/dL), Total bilirubin (mg/dL), LDH (u/L), Alk Phos (u/L), AST (u/L), Phosphorous (mg/dL), ALT (u/L), and G-GTP (u/L)

  • Immune Activation [ Time Frame: Cytokine release and signaling by CD4 lymphocytes were assessed once every 3 weeks for the duration of the study which lasted either 9 or 13 weeks. ] [ Designated as safety issue: No ]
    To assess whether the new crop of CD4 lymphocytes were immunocompetent, CD4 cells were harvested from blood and activated. This outcome measure was conducted only when the research subject had sufficient CD4 lymphocytes to perform the test. CD4 lymphocytes were stimulated using antibodies reactive with CD2, CD3, and CD28 for 3 days. Culture supernatant was measured for release of cytokines IL-2, IL-4, IL-10, and IFN gamma (pg/ml). Cells were harvested and examined for NFkB activation using flow cytometry which measured log fluorescence of stimulated cells as compared to unstimulated cells.

  • Extended Lymphocyte Phenotype [ Time Frame: the duration of the study lasting either 9 or 13 weeks. ] [ Designated as safety issue: No ]
    CD184, CD195, CD45RA, CD45RO, CD34 and CD25 (cells/ul) were assessed at the same time of day on the same day of the week each week.

  • Complete blood count and differential [ Time Frame: the duration of the study lasting either 9 or 13 weeks. ] [ Designated as safety issue: No ]
    Granulocytes, lymphocytes, monocytes, NK cells, basophils, and eosinophils (cells/ul) plus platelets (thousands/ul) were assessed at the same time of day on the same day of the week each week.


Enrollment: 4
Study Start Date: December 2006
Study Completion Date: February 2007
Primary Completion Date: February 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: alpha-1-Proteinase Inhibitor
Although Zemaira® (alpha-1-Proteinase Inhibitor) treatment is the standard treatment for patients with too little alpha-1-Proteinase Inhibitor, its use in HIV-1 patients has not been established. This pilot study was performed to show that Zemaira® treatment can be used in HIV-1 patients to elevate alpha-1-Proteinase Inhibitor and has the added benefit of elevating CD4 cells.
Biological: alpha-1-Proteinase Inhibitor
The Zemaira® dose used will depend on the patient's body weight. For example, a patient weighing 150 pounds would be infused with approximately ½ cup containing 8.4 grams of Zemaira®. Patients will be admitted to hospital for infusion. The I.V. infusion will be approximately 1 teaspoon/minute. Patients will receive weekly infusions of Zemaira® for 8 or 12 weeks. At the time of infusion, 40ml (3 Tablespoons) of blood will be collected (IRB approval #R04-003). The blood sample will be used to monitor viral load, CD4 cell numbers and function, cholesterol, triglycerides, LDL and HDL, and alpha-1-Proteinase Inhibitor.
Other Names:
  • Zemaira
  • Prolastin
Biological: alpha-1-Proteinase Inhibitor
The Zemaira® dose used was dependent on the patient's body weight. For example, a patient weighing 150 pounds was infused with approximately ½ cup containing 8.4 grams of Zemaira®. Patients were admitted to hospital for infusion. The I.V. infusion was approximately 1 teaspoon/minute. Patients received weekly infusions of Zemaira® 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 function, cholesterol, triglycerides, LDL and HDL, and alpha-1-Proteinase Inhibitor.
Other Names:
  • Prolastin
  • Zemaira
Biological: alpha-1-Proteinase Inhibitor
The Zemaira® dose was dependent on the patient's body weight. For example, a patient weighing 150 pounds was infused with approximately ½ cup containing 8.4 grams of Zemaira®. Patients were admitted to hospital for infusion. The I.V. infusion was approximately 1 teaspoon/minute. Patients received weekly infusions of Zemaira® 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 function, cholesterol, triglycerides, LDL and HDL, and alpha-1-Proteinase Inhibitor.
Other Name: Prolastin
Biological: alpha-1-Proteinase Inhibitor
The alpha-1-Proteinase Inhibitor dose used was dependent on the patient's body weight. For example, 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 function, cholesterol, triglycerides, LDL and HDL, and alpha-1-Proteinase Inhibitor.
Other Names:
  • Zemaira
  • Prolastin

Detailed Description:

HIV-1 patients were asked to participate in a pilot study to see whether the use of Zemaira® would increase blood levels of alpha-1-Proteinase Inhibitor and consequently increase CD4 cells. HIV-1 patients were specifically selected to receive Zemaira® therapy if they had <500 HIV-1 RNA copies/ml, <200 CD4 cells/ul, below normal alpha-1-Proteinase Inhibitor, and were on antiretroviral therapy and in general good health.

Patients received an I.V. infusion of Zemaira® once a week for 8 or 12 weeks and returned one week following the final infusion for blood collection. Each session lasted approximately 45 minutes. Each infusion was less than 30 minutes. At the time of infusion, patients were admitted to the hospital and 3 tablespoons of blood was collected. Blood was used to monitor viral load, CD4 cell numbers and function, cholesterol, triglycerides, LDL and HDL, and alpha-1-Proteinase Inhibitor levels.

  Eligibility

Ages Eligible for Study:   30 Years to 70 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients were selected if they had <500 HIV-1 RNA copies/ml, < 200 CD4 cells/ul, < 11uM alpha-1-Proteinase Inhibitor, were receiving antiretroviral therapy, and were in general good health.
  • Because of the small number of patients to be evaluated (n=4), only men were be included in the pilot study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01370018

Locations
United States, New York
Cabrini Medical Center
New York, New York, United States, 10003
Sponsors and Collaborators
Cabrini Medical Centre
CSL Behring
Investigators
Principal Investigator: Cynthia L Bristow, PhD Mount Sinai School of Medicine
Study Director: Jose Cortes, MD Beth Israel Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: Cynthia L. Bristow, PhD, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT01370018     History of Changes
Other Study ID Numbers: R06-005
Study First Received: June 6, 2011
Last Updated: June 8, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Cabrini Medical Centre:
CD4 counts

Additional relevant MeSH terms:
Alpha 1-Antitrypsin
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Serine Proteinase Inhibitors
Trypsin Inhibitors

ClinicalTrials.gov processed this record on October 21, 2014