HIV InfectionsPhase 2NCT00031070
Increasing HAART-Induced Immune Restoration With Cyclosporine
A Phase 2 study testing Abacavir sulfate, Lamivudine and Zidovudine, Cyclosporine and Hepatitis A Vaccine (Inactivated) in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 15 sites in United States.
Trial summary
The purpose of this study is to see if cyclosporine, taken when a patient begins highly active antiretroviral therapy (HAART), increases the number of CD4 T-cells (blood cells that fight infection) in a patient's blood. This study also will explore the safety of briefly giving cyclosporine to patients starting HAART. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- Abacavir sulfate, Lamivudine and Zidovudine, Cyclosporine and Hepatitis A Vaccine (Inactivated)
- Type of treatment
- Vaccines
- How many people
- 40 participants
- Where
- 15 sitesUnited States
- Study dates
- Start not givento Dec 2006
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients may be eligible for this study if they:
- Are HIV infected.
- Have received no more than 7 days of any anti-HIV treatment prior to study entry and not within 3 weeks of study entry.
- Have a CD4 cell count greater than 100 cells/mm3 within 30 days prior to study entry.
- Have a viral load greater than 5000 copies/ml within 30 days prior to study entry.
- Agree not to become pregnant or to impregnate during the study. The female/male partners must use 2 acceptable methods of contraception while receiving drugs and for 6 weeks after stopping the study drugs. Women and men who cannot have children do not need to use contraception.
Who cannot join
- Patients may not be eligible for this study if they:
- Have an AIDS-related infection or abnormal tissue growth within 1 year of study entry.
- Are pregnant or breast-feeding.
- Weigh less than 88 lbs (40 kg).
- Have taken 3TC or nonnucleoside reverse transcriptase inhibitors (NNRTIs).
- Have continuously taken for longer than 3 days any of the following prohibited drugs within 14 days before study entry: angiotensin-converting inhibitors, antibiotics, anticonvulsants, antihistamines, antineoplastics, antifungals, anti-inflammatory drugs, benzodiazepines, calcium channel blockers, gastrointestinal agents, systemic glucocorticoids, immunosuppressives, immunomodulators, potassium-sparing diuretics, statins, allopurinol, amiodarone, bromocryptine, danazol, digoxin, methotrexate, metoclopramide, octreotide, ticlopidine, orlistat, pimozide, nefazodone, fluvoxamine, and ergot derivatives.
Show all 15Show fewer
- Have taken St. John's wort, grapefruit, or grapefruit juice continuously for longer than 3 days within 14 days before study entry.
- Are allergic or sensitive to study HAART or cyclosporine.
- Abuse drugs or alcohol.
- Have autoimmune disease requiring immunosuppression.
- Have kidney disease or insufficiency.
- Have uncontrolled hypertension.
- Have migraines that require current continuous use of drugs.
- Have a seizure disorder that requires continuous use of anti-seizure drugs.
- Have an HLA B-57 haplotype (this gene has been associated with an increased chance for developing an allergic reaction to ABC).
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
University of Maryland, Institute of Human Virology
Baltimore, Maryland, 21201
Univ of North Carolina
Chapel Hill, North Carolina, 27599-7215
Univ of North Carolina / Infectious Disease Division
Chapel Hill, North Carolina, 27599
Rush Presbyterian - Saint Luke's Med Ctr / Infect Dis
Chicago, Illinois, 606123832
Rush Presbyterian - Saint Luke's Med Ctr
Chicago, Illinois, 60612
Case Western Reserve Univ
Cleveland, Ohio, 44106
MetroHealth Med Ctr
Cleveland, Ohio, 441091998
Univ of Texas Southwestern Med Ctr
Dallas, Texas, 75390
Univ of Texas, Southwestern Med Ctr of Dallas
Dallas, Texas, 75390
Indiana University Hospital
Indianapolis, Indiana, 46202-5250
University of Miami
Miami, Florida, 33136-1013
Univ of Minnesota
Minneapolis, Minnesota, 55455-0392
University of Pennsylvania, Philadelphia
Philadelphia, Pennsylvania, 19104
University of California , Davis Medical Center
Sacramento, California, 95814
Washington Univ (St. Louis)
St Louis, Missouri, 63108
About this study
Official title: Augmenting the Magnitude of HAART-Induced Immune Restoration With the Use of Cyclosporine
The purpose of this study is to see if cyclosporine, taken when a patient begins highly active antiretroviral therapy (HAART), increases the number of CD4 T-cells (blood cells that fight infection) in a patient's blood. This study also will explore the safety of briefly giving cyclosporine to patients starting HAART.
Read the detailed description
The availability of HAART has substantially decreased the morbidity and mortality caused by HIV-1 infection. There is clinical and laboratory evidence suggesting that treatment of HIV-1 infection not only arrests the progressive immune deterioration caused by HIV-1, but also is associated with at least partial immune reconstitution. After starting HAART, most patients with chronic HIV-1 infection experience an increase in CD4 T-cells, but the magnitude of CD4 lymphocyte rise is highly variable. Patients who do not experience a substantial rise in circulating CD4 lymphocytes remain at risk for opportunistic infections. Strategies to enhance immune restoration in HIV-1 disease are needed. Studies have shown that immune restoration after HAART in patients with chronic HIV-1 infection is incomplete. There are, however, several potential methods that can be used that possibly may enhance the magnitude of CD4 lymphocyte rise induced by HAART. It is proposed that the lymphoid tissues, in which lymphocytes are trapped and activated to die, are a major site of immunopathology and cellular losses in HIV-infection. Interference with lymphocyte trapping and death in lymphoid tissues when cyclosporine, an immunosuppressant, is administered at the time of initiation of HAART may result in an enhancement of the magnitude of cellular restoration in patients who initiate HAART.
Patients are randomized to 1 of 2 treatment arms:
Arm A: Weeks 1 to 2: abacavir (ABC)/lamivudine (3TC)/zidovudine (ZDV). Weeks 3 to 48: ABC/3TC/ZDV and efavirenz (EFV).
Arm B: Weeks 1 to 2: ABC/3TC/ZDV and cyclosporine. Weeks 3 to 48: ABC/3TC/ZDV and EFV.
Patients in both arms receive the following immunizations: Weeks 8 and 12: Hepatitis A vaccine inactivated and rabies vaccine.
Week 16: Rabies vaccine. To ascertain whether the augmentation in the rise in CD4 lymphocytes is sustained, the number of circulating CD4 lymphocytes 48 weeks after starting therapy is compared. To examine the functional significance of the cellular increases, the ability of patients to respond to immunization with recall and neoantigens are compared between the cyclosporine plus HAART arm and the HAART alone arm.
Substudy A5139: A 2-week substudy designed to explore the mechanisms of first-phase cellular restoration is performed. Patients undergo 4 lymph node aspirates. Lymphocytes are analyzed by the use of flow cytometry and correlated with findings in the main study. There is no limit on patient enrollment. Patients register to the substudy immediately after randomizing to the main study.
- Conditions
- HIV Infections
- Being tested
- Abacavir sulfate, Lamivudine and Zidovudine, Cyclosporine, Hepatitis A Vaccine (Inactivated), Efavirenz, Pneumococcal Conjugate Vaccine, Heptavalent
- Keywords
- Zidovudine, CD4 Lymphocyte Count, Lamivudine, Cyclosporine, Hepatitis A Vaccine, Rabies Vaccine, abacavir, Antiretroviral Therapy, Highly Active, efavirenz, Treatment Naive
- Medical subject headings
- HIV Infections, Hepatitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Abacavir sulfate, Lamivudine and ZidovudineDrug
CyclosporineDrug
Hepatitis A Vaccine (Inactivated)Biological
EfavirenzDrug
Pneumococcal Conjugate Vaccine, HeptavalentBiological
Rabies VaccineBiological
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2002 (estimated)
- Study completionDec 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Investigators
- Michael Lederman, M.D., Study chair, Case Western Reserve University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00031070
- Sponsor's protocol ID
- ACTG A5138
- Other IDs
- AACTG A5138, ACTG A5139s, AACTG A5139s
- Status last verified
- Aug 2006
- First submitted
- 20 Feb 2002
- Last updated
- 9 Mar 2015
- Results posted
- No
Publications
Lederman MM, Smeaton L, Smith KY, Rodriguez B, Pu M, Wang H, Sevin A, Tebas P, Sieg SF, Medvik K, Margolis DM, Pollard R, Ertl HC, Valdez H. Cyclosporin A provides no sustained immunologic benefit to persons with chronic HIV-1 infection starting suppressive antiretroviral therapy: results of a randomized, controlled trial of the AIDS Clinical Trials Group A5138. J Infect Dis. 2006 Dec 15;194(12):1677-85. doi: 10.1086/509261. Epub 2006 Nov 2.
PubMed 17109339
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Augmenting the Magnitude of HAART-Induced Immune Restoration With the Use of Cyclosporine
- ClinicalTrials.gov ID
- NCT00031070
- Acronym / sponsor ID
- ACTG A5138
- Conditions
- HIV Infections
- Keywords
- Zidovudine, CD4 Lymphocyte Count, Lamivudine, Cyclosporine, Hepatitis A Vaccine, Rabies Vaccine, abacavir, Antiretroviral Therapy, Highly Active
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study completion
- Dec 2006 (actual)
- First posted
- 22 Feb 2002 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to see if cyclosporine, taken when a patient begins highly active antiretroviral therapy (HAART), increases the number of CD4 T-cells (blood cells that fight infection) in a patient's blood. This study also will explore the safety of briefly giving cyclosporine to patients starting HAART.
Detailed description
The availability of HAART has substantially decreased the morbidity and mortality caused by HIV-1 infection. There is clinical and laboratory evidence suggesting that treatment of HIV-1 infection not only arrests the progressive immune deterioration caused by HIV-1, but also is associated with at least partial immune reconstitution. After starting HAART, most patients with chronic HIV-1 infection experience an increase in CD4 T-cells, but the magnitude of CD4 lymphocyte rise is highly variable. Patients who do not experience a substantial rise in circulating CD4 lymphocytes remain at risk for opportunistic infections. Strategies to enhance immune restoration in HIV-1 disease are needed. Studies have shown that immune restoration after HAART in patients with chronic HIV-1 infection is incomplete. There are, however, several potential methods that can be used that possibly may enhance the magnitude of CD4 lymphocyte rise induced by HAART. It is proposed that the lymphoid tissues, in which lymphocytes are trapped and activated to die, are a major site of immunopathology and cellular losses in HIV-infection. Interference with lymphocyte trapping and death in lymphoid tissues when cyclosporine, an immunosuppressant, is administered at the time of initiation of HAART may result in an enhancement of the magnitude of cellular restoration in patients who initiate HAART.
Patients are randomized to 1 of 2 treatment arms:
Arm A: Weeks 1 to 2: abacavir (ABC)/lamivudine (3TC)/zidovudine (ZDV). Weeks 3 to 48: ABC/3TC/ZDV and efavirenz (EFV).
Arm B: Weeks 1 to 2: ABC/3TC/ZDV and cyclosporine. Weeks 3 to 48: ABC/3TC/ZDV and EFV.
Patients in both arms receive the following immunizations: Weeks 8 and 12: Hepatitis A vaccine inactivated and rabies vaccine.
Week 16: Rabies vaccine. To ascertain whether the augmentation in the rise in CD4 lymphocytes is sustained, the number of circulating CD4 lymphocytes 48 weeks after starting therapy is compared. To examine the functional significance of the cellular increases, the ability of patients to respond to immunization with recall and neoantigens are compared between the cyclosporine plus HAART arm and the HAART alone arm.
Substudy A5139: A 2-week substudy designed to explore the mechanisms of first-phase cellular restoration is performed. Patients undergo 4 lymph node aspirates. Lymphocytes are analyzed by the use of flow cytometry and correlated with findings in the main study. There is no limit on patient enrollment. Patients register to the substudy immediately after randomizing to the main study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Are HIV infected.
- Have received no more than 7 days of any anti-HIV treatment prior to study entry and not within 3 weeks of study entry.
- Have a CD4 cell count greater than 100 cells/mm3 within 30 days prior to study entry.
- Have a viral load greater than 5000 copies/ml within 30 days prior to study entry.
- Agree not to become pregnant or to impregnate during the study. The female/male partners must use 2 acceptable methods of contraception while receiving drugs and for 6 weeks after stopping the study drugs. Women and men who cannot have children do not need to use contraception.
Key exclusion criteria (15 listed)
- Have an AIDS-related infection or abnormal tissue growth within 1 year of study entry.
- Are pregnant or breast-feeding.
- Weigh less than 88 lbs (40 kg).
- Have taken 3TC or nonnucleoside reverse transcriptase inhibitors (NNRTIs).
- Have continuously taken for longer than 3 days any of the following prohibited drugs within 14 days before study entry: angiotensin-converting inhibitors, antibiotics, anticonvulsants, antihistamines, antineoplastics, antifungals, anti-inflammatory drugs, benzodiazepines, calcium channel blockers, gastrointestinal agents, systemic glucocorticoids, immunosuppressives, immunomodulators, potassium-sparing diuretics, statins, allopurinol, amiodarone, bromocryptine, danazol, digoxin, methotrexate, metoclopramide, octreotide, ticlopidine, orlistat, pimozide, nefazodone, fluvoxamine, and ergot derivatives.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Abacavir sulfate, Lamivudine and Zidovudine | Drug | – |
| Cyclosporine | Drug | – |
| Hepatitis A Vaccine (Inactivated) | Biological | – |
| Efavirenz | Drug | – |
| Pneumococcal Conjugate Vaccine, Heptavalent | Biological | – |
| Rabies Vaccine | Biological | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2015.
- Derived from this study: PubMed 17109339Lederman MM, Smeaton L, Smith KY, Rodriguez B, Pu M, Wang H, Sevin A, Tebas P, Sieg SF, Medvik K, Margolis DM, Pollard R, Ertl HC, Valdez H. Cyclosporin A provides no sustained immunologic benefit to persons with chronic HIV-1 infection starting suppressive antiretroviral therapy: results of a randomized, controlled trial of the AIDS Clinical Trials Group A5138. J Infect Dis. 2006 Dec 15;194(12):1677-85. doi: 10.1086/509261. Epub 2006 Nov 2.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Lederman, M.D. study chair
Case Western Reserve University
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Abacavir sulfate, Lamivudine and Zidovudine, Cyclosporine and Hepatitis A Vaccine (Inactivated) in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 15 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00031070, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2015.