HIV InfectionsPhase 1HIV-HAARTNCT00157027
RHIV A Pilot Study Refractory or Intolerant to Highly Active Antiretroviral Therapy (HAART)
A Phase 1 study testing Extracorporeal photochemotherapy with UVADEX in people with HIV Infections, run by Atlantic Health System.
Trial summary
The objectives of this clinical trial are to: Assess the safety of using extracorporeal photoimmune therapy with the photosensitizing agent Uvadex in the treatment of HIV-1 infection; Evaluate the effects of this therapy on HIV-1 viral load by polymerase chain reaction (PCR) analysis; Evaluate the effects of this… 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?
- Extracorporeal photochemotherapy with UVADEX
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Dec 2003to Apr 2010
- Phase
- Phase 1
- 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
- HIV-1 positive by ELISA assay and confirmed by Western blot
- Patients must be refractory or intolerant to HAART. Refractory HIV patients are defined as those patients meeting the following criteria:
- Resistance to all major groups of active agents (non-nucleotide reverse transcriptase inhibitors [NNRTIs], nucleotide reverse transcriptase inhibitors [NRTIs], and protease inhibitors [PIs]);
- Not achieving < 400 copies/mL by 24 weeks or < 50 copies/mL by 48 weeks of therapy; or
- Documentation of resistance mutations by genotype testing; or
- Failure to increase CD4+ cells > 25 cells/mm3 above baseline after one year of therapy.
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- HIV RNA >= 3,000 copies/mL by PCR analysis
- CD4 count > 75 cells/mm3
- No new antiretroviral agents may be added during the pre-study evaluation, treatment, or follow-up periods.
- Life expectancy > 6 months
- Able to give informed consent and comply with all study visits, procedures, and the ECP treatment schedule
- Ages between 18 and 70
- Females of childbearing potential may not be lactating and must be human chorionic gonadotropin (HCG) negative at study entry and agree to use acceptable methods of birth control (hormonal, intrauterine device, and spermicide and barrier) throughout the study period.
- Minimum body weight of 88 lbs (40kg)
- May not have current photosensitive diseases such as systemic lupus erythematosus (SLE) or porphyria
- Adequate hematological function with an absolute neutrophil count of >= 500/mm and a platelet count of >= 50,000/mm.
Who cannot join
- Established history of heparin or psoralen allergy
- Patients with aphakia because of significantly increased risk of retinal damage due to absence of lenses. Patients with lens implants are acceptable for inclusion.
- Current participation (within 30 days) in a clinical trial examining the safety and/or efficacy of anti-retroviral agent(s)
- Patients with any other major illness (e.g. malignancy, renal failure, severe cardiac disease, severe neurologic disease) that either might preclude completion of the study or bias efficacy assessments.
- Patients who cannot or may not tolerate the extracorporeal volume required during the procedure, for reasons such as severe cardiovascular disease, i.e. history of congestive heart failure or severe anemia (hemoglobin < 90 g/L)
- Patients with a photosensitive disease, such as porphyria or systemic lupus erythematosus. Special care must be taken in the treatment of patients who require medications (either topically or systemically) during the course of the study with photosensitizing potential, such as phenothiazine, tetracyclines, sulfonamides, some non-steroidal anti-inflammatory drugs (NSAIDs) or chlorothiazide. Patients who must take photosensitizing drugs during the study will not receive them within 24 hours of each scheduled treatment.
About this study
Official title: The Use of Extracorporeal Photochemotherapy With UVADEX in Patients With HIV Who Are Refractory or Intolerant to HAART
The objectives of this clinical trial are to:
- Assess the safety of using extracorporeal photoimmune therapy with the photosensitizing agent Uvadex in the treatment of HIV-1 infection;
- Evaluate the effects of this therapy on HIV-1 viral load by polymerase chain reaction (PCR) analysis;
- Evaluate the effects of this therapy on CD4+, CD8+ cells and CD4/CD8 ratio;
- Evaluate the effects of this therapy on the patient's immune system, by skin reactivity to a standard anergy panel.
Read the detailed description
Rationale for the Use of ECP with UVADEX in Patients with HIV-1 Infection
Studies have demonstrated that psoralen and ultraviolet A light inactivate HIV virus in vitro. Edelson, et al, showed that extracorporeal photochemotherapy (ECP) with psoralen primarily targets the CD4+ cell, the population predominately affected by HIV-1 infection. It is postulated that the re-infusion of the ECP treated cell fraction, free virus, cell-associated virus along with whole cells, cell fragments, and soluble antigens, may serve to engender a specific HIV immune response.
A twenty-patient study using ECP with psoralen was conducted by Bisaccia, et al. In this study, patients were HIV positive by enzyme linked immunosorbent assay and these positive results were confirmed by Western blot test. Patients were staged as Walter Reed class WR3 to WR5. Extracorporeal photoimmune therapy was administered on two consecutive days on a monthly basis for 6-29 months. This study reported that CD4 counts declined more slowly than historical controls. Walter Reed classification improved in 55% (11/20), was stable in 35% (7/20) and declined in 10% (2/20) of the patients treated in this study.
One measure in the "in vivo" evaluation of T-cell function is provided by skin reactivity to recall antigens (DTH). A lack of this response has been associated with progression of HIV disease. In the Bisaccia study, skin reactivity to recall antigens (DTH) improved in 55% (11/20) patients, were stable in 35% (7/20), progressed to anergy in 5% (1/20). One patient was initially anergic and remained anergic post-treatment. Following treatment with ECP, 60% (9/15), displayed normal skin test responses, whereas the baseline examinations had been normal in only 5% (1/19). In addition, 21% (4/19) of patients showed a partial skin test response. Only 10% (2/20) of patients developed a new opportunistic infection. This included the patient initially anergic and who remained anergic and the patient who progressed to anergy post-ECP treatment.
DESCRIPTION OF THE UVAR® XTSÔ PHOTOPHERESIS SYSTEM
Photopheresis (or extracorporeal photoimmune therapy [ECP]) is a process developed by THERAKOS, Inc., a Johnson and Johnson Company. During the process of ECP, whole blood is drawn from the patient over several cycles, centrifuged and separated into the components of plasma, white cells (or buffy coat), and red blood cells. A portion of the white cells and the plasma are saved in a separate compartment. The remaining plasma and red blood cells are immediately returned to the patient.
The saved buffy coat (white blood cells) and plasma are inoculated with the photosensitizing agent UVADEX. Photoactivation begins when the suspension is exposed to a prescribed amount of ultraviolet-A light. After photoactivation is complete, the treated suspension is returned to the patient.
Photopheresis performed using the UVAR XTS is a continuous process. During the entire therapy, the patient remains connected to the photopheresis instrument. The duration of time between completion of the buffy coat collection and reinfusion of the light-activated buffy coat is approximately 30 minutes.
- Conditions
- HIV Infections
- Being tested
- Extracorporeal photochemotherapy with UVADEX
- Keywords
- Treatment Experienced, HIV-1 Positive by ELISA Assay, Confirmed by Western Blot, Refractory or intolerant to HAART
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Extracorporeal photochemotherapy with UVADEXProcedure or surgery
Photopheresis (or extracorporeal photoimmunetherapy [ECP]) is a process developed by THERAKOS, Inc., a Johnson and Johnson Company. During the process of ECP, whole blood is drawn from the patient over several cycles, centrifuged and separated into the components of plasma, white cells (or buffy coat), and red blood cells. A portion of the white cells and the plasma are saved in a separate compartment. The remaining plasma and red blood cells are immediately returned to the patient.
The saved buffy coat (white blood cells) and plasma are inoculated with the photosensitizing agent UVADEX. Photoactivation begins when the suspension is exposed to a prescribed amount of ultraviolet-A light. After photoactivation is complete, the treated suspension is returned to the patient.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Photopheresis (or extracorporeal photoimmunetherapy [ECP]) is a process developed by THERAKOS, Inc., a Johnson and Johnson Company. During the process of ECP, whole blood is drawn from the patient over several cycles, centrifuged and separated into the components of plasma, white cells (or buffy coat), and red blood cells. A portion of the white cells and the plasma are saved in a separate compartment. The remaining plasma and red blood cells are immediately returned to the patient.
The saved buffy coat (white blood cells) and plasma are inoculated with the photosensitizing agent UVADEX. Photoactivation begins when the suspension is exposed to a prescribed amount of ultraviolet-A light. After photoactivation is complete, the treated suspension is returned to the patient. Receives: Procedure: Extracorporeal photochemotherapy with UVADEX |
What is being measured
The primary outcome is the main question the study is designed to answer.
evaluate the effects of this therapy on HIV-1 viral load by PCR analysis
Measured: 9 months
evaluate the effects of this therapy on CD4+, CD8+ cells and CD4/CD8 ratio
Measured: 9 months
evaluate the effects of this therapy on the patient's immune system, by skin reactivity to a standard anergy panel
Measured: 9 months
The objectives of this clinical trial are to: assess the safety of using extracorporeal photoimmune therapy with the photosensitizing agent UVADEX in the treatment of HIV-1 infection.
Measured: 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2005 (estimated)
- Study startDec 2003
- Study completionApr 2010 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Atlantic Health System
- Sponsor type
- University, hospital or other
- Collaborators
- Therakos
- Investigators
- Emil Bisaccia, MD, Principal investigator, Morristown Memorial Hospital-Atlantic Health System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00157027
- Sponsor's protocol ID
- R03-05-012
- Acronym
- HIV-HAART
- Status last verified
- Jan 2014
- First submitted
- 8 Sep 2005
- Last updated
- 16 Jan 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Use of Extracorporeal Photochemotherapy With UVADEX in Patients With HIV Who Are Refractory or Intolerant to HAART
- ClinicalTrials.gov ID
- NCT00157027
- Acronym / sponsor ID
- HIV-HAART / R03-05-012
- Conditions
- HIV Infections
- Keywords
- Treatment Experienced, HIV-1 Positive by ELISA Assay, Confirmed by Western Blot, Refractory or intolerant to HAART
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Atlantic Health SystemUniversity, hospital or other
- Collaborators
- Therakos
- Study start
- Dec 2003
- Study completion
- Apr 2010 (estimated)
- First posted
- 12 Sep 2005 (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 objectives of this clinical trial are to:
- Assess the safety of using extracorporeal photoimmune therapy with the photosensitizing agent Uvadex in the treatment of HIV-1 infection;
- Evaluate the effects of this therapy on HIV-1 viral load by polymerase chain reaction (PCR) analysis;
- Evaluate the effects of this therapy on CD4+, CD8+ cells and CD4/CD8 ratio;
- Evaluate the effects of this therapy on the patient's immune system, by skin reactivity to a standard anergy panel.
Detailed description
Rationale for the Use of ECP with UVADEX in Patients with HIV-1 Infection
Studies have demonstrated that psoralen and ultraviolet A light inactivate HIV virus in vitro. Edelson, et al, showed that extracorporeal photochemotherapy (ECP) with psoralen primarily targets the CD4+ cell, the population predominately affected by HIV-1 infection. It is postulated that the re-infusion of the ECP treated cell fraction, free virus, cell-associated virus along with whole cells, cell fragments, and soluble antigens, may serve to engender a specific HIV immune response.
A twenty-patient study using ECP with psoralen was conducted by Bisaccia, et al. In this study, patients were HIV positive by enzyme linked immunosorbent assay and these positive results were confirmed by Western blot test. Patients were staged as Walter Reed class WR3 to WR5. Extracorporeal photoimmune therapy was administered on two consecutive days on a monthly basis for 6-29 months. This study reported that CD4 counts declined more slowly than historical controls. Walter Reed classification improved in 55% (11/20), was stable in 35% (7/20) and declined in 10% (2/20) of the patients treated in this study.
One measure in the "in vivo" evaluation of T-cell function is provided by skin reactivity to recall antigens (DTH). A lack of this response has been associated with progression of HIV disease. In the Bisaccia study, skin reactivity to recall antigens (DTH) improved in 55% (11/20) patients, were stable in 35% (7/20), progressed to anergy in 5% (1/20). One patient was initially anergic and remained anergic post-treatment. Following treatment with ECP, 60% (9/15), displayed normal skin test responses, whereas the baseline examinations had been normal in only 5% (1/19). In addition, 21% (4/19) of patients showed a partial skin test response. Only 10% (2/20) of patients developed a new opportunistic infection. This included the patient initially anergic and who remained anergic and the patient who progressed to anergy post-ECP treatment.
DESCRIPTION OF THE UVAR® XTSÔ PHOTOPHERESIS SYSTEM
Photopheresis (or extracorporeal photoimmune therapy [ECP]) is a process developed by THERAKOS, Inc., a Johnson and Johnson Company. During the process of ECP, whole blood is drawn from the patient over several cycles, centrifuged and separated into the components of plasma, white cells (or buffy coat), and red blood cells. A portion of the white cells and the plasma are saved in a separate compartment. The remaining plasma and red blood cells are immediately returned to the patient.
The saved buffy coat (white blood cells) and plasma are inoculated with the photosensitizing agent UVADEX. Photoactivation begins when the suspension is exposed to a prescribed amount of ultraviolet-A light. After photoactivation is complete, the treated suspension is returned to the patient.
Photopheresis performed using the UVAR XTS is a continuous process. During the entire therapy, the patient remains connected to the photopheresis instrument. The duration of time between completion of the buffy coat collection and reinfusion of the light-activated buffy coat is approximately 30 minutes.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Procedure: Extracorporeal photochemotherapy with UVADEXPhotopheresis (or extracorporeal photoimmunetherapy [ECP]) is a process developed by THERAKOS, Inc., a Johnson and Johnson Company. During the process of ECP, whole blood is drawn from the patient over several cycles, centrifuged and separated into the components of plasma, white cells (or buffy coat), and red blood cells. A portion of the white cells and the plasma are saved in a separate compartment. The remaining plasma and red blood cells are immediately returned to the patient. The saved buffy coat (white blood cells) and plasma are inoculated with the photosensitizing agent UVADEX. Photoactivation begins when the suspension is exposed to a prescribed amount of ultraviolet-A light. After photoactivation is complete, the treated suspension is returned to the patient. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- HIV-1 positive by ELISA assay and confirmed by Western blot
- Patients must be refractory or intolerant to HAART. Refractory HIV patients are defined as those patients meeting the following criteria:
- HIV RNA >= 3,000 copies/mL by PCR analysis
- CD4 count > 75 cells/mm3
- No new antiretroviral agents may be added during the pre-study evaluation, treatment, or follow-up periods.
Key exclusion criteria (6 listed)
- Established history of heparin or psoralen allergy
- Patients with aphakia because of significantly increased risk of retinal damage due to absence of lenses. Patients with lens implants are acceptable for inclusion.
- Current participation (within 30 days) in a clinical trial examining the safety and/or efficacy of anti-retroviral agent(s)
- Patients with any other major illness (e.g. malignancy, renal failure, severe cardiac disease, severe neurologic disease) that either might preclude completion of the study or bias efficacy assessments.
- Patients who cannot or may not tolerate the extracorporeal volume required during the procedure, for reasons such as severe cardiovascular disease, i.e. history of congestive heart failure or severe anemia (hemoglobin < 90 g/L)
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 |
|---|---|---|
| Extracorporeal photochemotherapy with UVADEXPhotopheresis (or extracorporeal photoimmunetherapy [ECP]) is a process developed by THERAKOS, Inc., a Johnson and Johnson Company. During the process of ECP, whole blood is drawn from the patient over several cycles, centrifuged and separated into the components of plasma, white cells (or buffy coat), and red blood cells. A portion of the white cells and the plasma are saved in a separate compartment. The remaining plasma and red blood cells are immediately returned to the patient. The saved buffy coat (white blood cells) and plasma are inoculated with the photosensitizing agent UVADEX. Photoactivation begins when the suspension is exposed to a prescribed amount of ultraviolet-A light. After photoactivation is complete, the treated suspension is returned to the patient. | Procedure or surgery | 1 |
Primary outcome
evaluate the effects of this therapy on HIV-1 viral load by PCR analysis
Time frame: 9 months
evaluate the effects of this therapy on CD4+, CD8+ cells and CD4/CD8 ratio
Time frame: 9 months
evaluate the effects of this therapy on the patient's immune system, by skin reactivity to a standard anergy panel
Time frame: 9 months
The objectives of this clinical trial are to: assess the safety of using extracorporeal photoimmune therapy with the photosensitizing agent UVADEX in the treatment of HIV-1 infection.
Time frame: 9 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2014.
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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.
Emil Bisaccia, MD principal investigator
Morristown Memorial Hospital-Atlantic Health System
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Extracorporeal photochemotherapy with UVADEX in people with HIV Infections, run by Atlantic Health System.
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 16 inclusion and 6 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: withdrawn, as of the sponsor's last update on 16 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 was withdrawn before enrolling participants, so there are no results.
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.
What does the primary outcome measure?
evaluate the effects of this therapy on HIV-1 viral load by PCR analysis (time frame: 9 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Jan 2014.