HIV Infections Clinical Trial
Official title:
Anakinra, a Recombinant Human IL-1 Receptor Antagonist for Neuroinflammation in HIV-1 Infection
Verified date | March 2, 2018 |
Source | National Institutes of Health Clinical Center (CC) |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Background:
HIV can sometimes cause HIV-associated neurocognitive disorder, or HAND. HAND is
HIV-associated neurocognitive disorder. It can affect memory, thinking, or concentration. It
can cause mood changes. HAND may be caused by HIV hiding in the central nervous system then
causing inflammation. Researchers want to see if a drug for inflammation (Anakinra) can help
people with HIV.
Objective:
To see if a drug for inflammatory diseases is safe for people with HIV-infection on
antiretroviral therapy.
Eligibility:
Adults 18-61 years old with HIV who are enrolled in another study.
Design:
Participants will be screened with medical history, physical exam, and blood and urine tests.
Participants will have up to 15 study visits over 16 weeks.
At study visit 1, participants will have:
- Screening tests repeated.
- Brain magnetic resonance imaging (MRI) scans. They will lie on a table that slides into
a metal cylinder in a strong magnetic field. They will get a dye inserted by a thin
plastic tube in a vein.
- Lumbar puncture. The lower back will be numbed. A needle will collect fluid from between
bones in the back.
- Tests of memory, thinking, and attention. Participants may also fill out forms and do
tasks.
Participants will learn how to inject the study drug. Over 8 weeks, they will give themselves
the study drug at home every day. They will do up to 3 injections at once. They will write
down their injections and any side effects.
Participants will have 5 weekly visits while taking the study drug. They will answer
questions and have blood drawn.
At weeks 8 and 16, they will have a visit that repeats visit 1.
Status | Terminated |
Enrollment | 1 |
Est. completion date | March 2, 2018 |
Est. primary completion date | March 2, 2018 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 61 Years |
Eligibility |
- INCLUSION CRITERIA - Age 18-61 years old - Laboratory-confirmed HIV-1 infection - CD4 count >350 cells/mm^3 - Plasma HIV RNA <50 copies/mL for at least 12 months prior to screening. Participants who have a viral blip of up to 200 copies/mL may be included if they have a preceding and following VL <50 copies/mL. - Stable antiretroviral therapy regimen for greater than or equal to 3 months prior to screening - Weight greater than or equal to 50 kg - Have participated in NIH protocol 13 N-0149 or the JHU Clinical Outcomes Core - Completion of at least 7th grade (according to subject report) and ability to speak, read, and understand English to allow use of standard neurocognitive batteries - An established primary care provider - Willingness to have blood and CSF samples stored for future research - Willingness to undergo serial lumbar punctures (LPs) per study schedule - Willingness to undergo genetic testing - For women of childbearing potential, willingness to use 2 forms of effective birth control beginning 2 weeks before and continuing until 12 weeks after the start of anakinra. One method must be a condom and the other may be a diaphragm or cervical cap with spermicide, oral contraceptive, implant, contraceptive patch, IUD placed at least 3 months ago or having a male partner who had a vasectomy at least 3 months ago. EXCLUSION CRITERIA - Presence of a neurologic condition that would confound study evaluations (eg, multiple sclerosis, Parkinson s disease). Neurologic conditions that would not interfere with study evaluations (eg, migraine, peripheral neuropathy) will be allowed. - Presence of a condition, other than HAND, associated with cognitive impairment (e.g. untreated severe sleep apnea) at screening - Presence of HIV-associated dementia as determined through participation in NIH protocol 13-N-0149 or the JHU Clinical Outcomes Core - Inability to provide informed consent - Past or current psychiatric illness that may interfere with protocol adherence (eg schizophrenia or bipolar disorder) - Use of any psychiatric medications unless stable greater than or equal to 3 months at the time of screening - Current asthma requiring treatment - History of any AIDS-defining opportunistic infection in the past two years or any history of a CNS opportunistic infection - History of lymphoma or melanoma - Any medical condition (eg, congestive heart failure, coronary artery disease, chronic obstructive pulmonary disease, severe osteoarthritis) that would make frequent study visits and travel difficult for the participant - Positive urine drug screen or active abuse of illegal drugs, narcotics or alcohol as determined by the study investigator at the time of screening or at baseline evaluations - Women who are pregnant or actively seeking to become pregnant - Women who are breastfeeding - Use of any systemic immunosuppressive medication, including TNF inhibitors, within five half lives of the drug prior to of screening - Contraindications to LP including: International Normalized Ratio (INR) >1.5, platelets <100,000/Microlitre, or inability to temporarily discontinue aspirin for 7-10 days and nonsteroidal anti-inflammatory drugs for 3 days prior to LP - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5x laboratory upper limit of normal - Absolute neutrophil count <1000/mm^3 or hemoglobin <10mg/dL - Estimated glomerular filtration rate <60 mL/min or a history of renal dialysis - Other laboratory abnormality that would make the study risky for the patient as determined by the study investigator - Acute or chronic hepatitis C virus infection determined by a detectable VL - Acute or chronic hepatitis B determined by detectable hepatitis B surface antigen (HbsAg) or hepatitis B core antibody (HbcAb) IgM - History of tuberculosis (TB), or positive TB test at screening (QuantiFERON or tuberculin skin test) - Other infection (eg, influenza, urinary tract infection) that would affect response to anakinra, or that would represent a risk of significant infection based upon the known effects of anakinra, and the likely effects of anakinra on this population. - Receipt of live vaccine within four weeks of starting anakinra or planned within three months after study completion - Contraindication to MRI including pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, some types of aneurysm clips (metal clips on the wall of a large artery), some types of metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, or shrapnel fragments. Participants who require sedation for claustrophobia during the MRI will not be excluded. - Known hypersensitivity or contraindication to gadolinium or any component of anakinra - Participation in a clinical protocol (e.g. anti-inflammatory drug intervention study) which includes an intervention that may affect the results of the current study. - Any condition that would increase risk to the subject or would interfere with the subject s ability to comply with protocol requirements (e.g. inability to travel to the study site frequently). |
Country | Name | City | State |
---|---|---|---|
United States | Johns Hopkins University | Baltimore | Maryland |
United States | National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland |
Lead Sponsor | Collaborator |
---|---|
National Institute of Neurological Disorders and Stroke (NINDS) | Johns Hopkins University |
United States,
Andersson LM, Hagberg L, Rosengren L, Fuchs D, Blennow K, Gisslén M. Normalisation of cerebrospinal fluid biomarkers parallels improvement of neurological symptoms following HAART in HIV dementia--case report. BMC Infect Dis. 2006 Sep 15;6:141. — View Citation
Robertson KR, Smurzynski M, Parsons TD, Wu K, Bosch RJ, Wu J, McArthur JC, Collier AC, Evans SR, Ellis RJ. The prevalence and incidence of neurocognitive impairment in the HAART era. AIDS. 2007 Sep 12;21(14):1915-21. — View Citation
Simioni S, Cavassini M, Annoni JM, Rimbault Abraham A, Bourquin I, Schiffer V, Calmy A, Chave JP, Giacobini E, Hirschel B, Du Pasquier RA. Cognitive dysfunction in HIV patients despite long-standing suppression of viremia. AIDS. 2010 Jun 1;24(9):1243-50. doi: 10.1097/QAD.0b013e3283354a7b. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Frequency and severity of AEs and SAEs | Day 56, Day 112 | ||
Primary | Frequency of increases in HIV viral load to greater than or equal to 500 copies/mL on 2 consecutive measurements | Day 56, Day 112 | ||
Secondary | Changes in neurocognitive and neurobehavioral function after 8 weeks | Day 56, Day 112 | ||
Secondary | Changes in systemic inflammatory biomarkers in plasma after 8 weeks of anakinra and then 8 weeks later | Day 56, Day 112 | ||
Secondary | Changes in CNS inflammatory and injury biomarkers in CSF and on MRI after 8 weeks of anakinra and then 8 weeks later | Day 56, Day 112 |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT05454514 -
Automated Medication Platform With Video Observation and Facial Recognition to Improve Adherence to Antiretroviral Therapy in Patients With HIV/AIDS
|
N/A | |
Completed |
NCT03760458 -
The Pharmacokinetics, Safety, and Tolerability of Abacavir/Dolutegravir/Lamivudine Dispersible and Immediate Release Tablets in HIV-1-Infected Children Less Than 12 Years of Age
|
Phase 1/Phase 2 | |
Completed |
NCT03141918 -
Effect of Supplementation of Bioactive Compounds on the Energy Metabolism of People Living With HIV / AIDS
|
N/A | |
Completed |
NCT03067285 -
A Phase IV, Open-label, Randomised, Pilot Clinical Trial Designed to Evaluate the Potential Neurotoxicity of Dolutegravir/Lamivudine/Abacavir in Neurosymptomatic HIV Patients and Its Reversibility After Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide. DREAM Study
|
Phase 4 | |
Recruiting |
NCT04579146 -
Coronary Artery Disease (CAD) in Patients HIV-infected
|
||
Completed |
NCT06212531 -
Papuan Indigenous Model of Male Circumcision
|
N/A | |
Active, not recruiting |
NCT03256422 -
Antiretroviral Treatment Taken 4 Days Per Week Versus Continuous Therapy 7/7 Days Per Week in HIV-1 Infected Patients
|
Phase 3 | |
Completed |
NCT03256435 -
Retention in PrEP Care for African American MSM in Mississippi
|
N/A | |
Completed |
NCT00517803 -
Micronutrient Supplemented Probiotic Yogurt for HIV/AIDS and Other Immunodeficiencies
|
N/A | |
Active, not recruiting |
NCT03572335 -
Systems Biology of Diffusion Impairment in Human Immunodeficiency Virus (HIV)
|
||
Completed |
NCT04165200 -
Fecal Microbiota Transplantation as a Therapeutic Strategy for Patients Infected With HIV
|
N/A | |
Recruiting |
NCT03854630 -
Hepatitis B Virus Vaccination in HIV-positive Patients and Individuals at High Risk for HIV Infection
|
Phase 4 | |
Terminated |
NCT03275571 -
HIV, Computerized Depression Therapy & Cognition
|
N/A | |
Completed |
NCT02234882 -
Study on Pharmacokinetics
|
Phase 1 | |
Completed |
NCT01618305 -
Evaluating the Response to Two Antiretroviral Medication Regimens in HIV-Infected Pregnant Women, Who Begin Antiretroviral Therapy Between 20 and 36 Weeks of Pregnancy, for the Prevention of Mother-to-Child Transmission
|
Phase 4 | |
Recruiting |
NCT05043129 -
Safety and Immune Response of COVID-19 Vaccination in Patients With HIV Infection
|
||
Not yet recruiting |
NCT05536466 -
The Influence of Having Bariatric Surgery on the Pharmacokinetics, Safety and Efficacy of the Novel Non-nucleoside Reverse Transcriptase Inhibitor Doravirine
|
N/A | |
Recruiting |
NCT04985760 -
Evaluation of Trimer 4571 Therapeutic Vaccination in Adults Living With HIV on Suppressive Antiretroviral Therapy
|
Phase 1 | |
Completed |
NCT05916989 -
Stimulant Use and Methylation in HIV
|
||
Terminated |
NCT02116660 -
Evaluation of Renal Function, Efficacy, and Safety When Switching From Tenofovir/Emtricitabine Plus a Protease Inhibitor/Ritonavir, to a Combination of Raltegravir (MK-0518) Plus Nevirapine Plus Lamivudine in HIV-1 Participants With Suppressed Viremia and Impaired Renal Function (MK-0518-284)
|
Phase 2 |