HERV-K Suppression Using Antiretroviral Therapy in Volunteers With Amyotrophic Lateral Sclerosis (ALS)

150126

Background: Some people with Amyotrophic Lateral Sclerosis (ALS) have a high level of the virus HERV-K in their blood. Researchers do not think this virus causes ALS. But they don t know why some people with ALS have a high level of it. They want to know if HERV-K can be suppressed by drugs that are used to treat HIV infection. Objectives: To learn how drugs usually taken for HIV infection affect people with Amyotrophic Lateral Sclerosis (ALS). Eligibility: Adults at least 18 years old with ALS and high levels of HERV-K but no HIV. Design: Interested participants can contact the study team and, if eligible, the study team will arrange for a screening blood draw to determine the HERV-K level. Participants with a high HERV-K level will be screened with medical history, physical exam, questionnaires, nerve conduction test, lumbar puncture, and blood and breathing tests. After screening, participants will start taking the 4 study drugs. Participants will have up to 12 study visits over a period of 72 weeks. After starting study drugs, they will have study visits at Weeks 1 and 4 and then every 4 weeks until Week 28. They will be asked how they are feeling and have an exam and blood drawn. At 3 visits, they will have tests of nerve conduction, breathing, and their ALS symptoms. At Week 24, they will stop taking the study drugs and may have a repeat lumbar puncture. After the Week 48 visit, their participation is finished.

2019-04-01

2022-11-17

2023-05-09

Completed

Early phase I

122

INCLUSION CRITERIA: Subjects must meet all of the following inclusion criteria to be eligible to participate in this study: Age 18 years or older at the time of the screening visit. Able to provide informed consent and comply with study procedures. ALS diagnosed as probable, laboratory-supported probable or definite according to the World Federation of Neurology El Escorial revised criteria as determined by a neurologist with neuromuscular subspecialty training. A ratio of HERV-K:RPP greater than or equal to 13 measured by quantitative PCR at the screening visit. Duration of disease less than 2 years, or if greater than 2 years, disease progression at a rate that in the judgement of the investigator would allow for completion of the study. If taking riluzole or edaravone, must be on a stable dose for at least 30 days prior to the screening visit, or stopped taking riluzole or edaravone at least 30 days prior to the screening visit. Subject has a competent caregiver who can and will be responsible for administering study drug. If there is no caregiver, another qualified individual must be available to do this. Subject has established care with a neurologist and will maintain this clinical care throughout the study. Subject has had neuroimaging within the last 24 months for participants enrolling at the NIH Clinical Center. EXCLUSION CRITERIA: A participant will be excluded if he or she has any of the following: Dependence on daytime mechanical ventilation (invasive or non-invasive, including Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BiPap) at the time of the screening visit. Participation in any other investigational drug trial or using investigational drug (within 4 weeks prior to the Day 0 visit and thereafter). History of severe sulfonamide allergy (i.e. anaphylaxis). History of positive test or positive result at screening for HIV or HTLV-1. Participants must not be able to become pregnant (e.g., post-menopausal for at least one year, surgically sterile, or using adequate methods of contraception) or breastfeed for the duration of the study. Adequate methods of contraception include: implanted contraception, intrauterine device in place for at least 3 months, or barrier method in conjunction with spermicide. Participants of childbearing potential must have a negative pregnancy test at screening and be non-lactating. Presence of any of the following clinical conditions at the time of screening: Drug abuse or alcoholism Unstable medical disease (such as unstable angina or chronic obstructive pulmonary disease), or active infectious disease (such as Hepatitis C or tuberculosis), or current malignancy Unstable psychiatric illness defined as psychosis or untreated major depression within 90 days of the screening visit Dementia Diabetes mellitus Hemophilia Use of contraindicated medications: amiodarone, dronedarone, lovastatin, simvastatin, rifampin, rifapentine, rifabutin, cisapride, pimozide, midazolam, triazolam, dihydroergotamine, ergonovine, ergotamine, methylergonovine, St. John s wort, alfuzosin, salmeterol, sildenafil for pulmonary arterial hypertension, oxcarbazepine, phenobarbital, phenytoin or dofetilide. Safety Laboratory Criteria at the screening visit: Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3.0 times the upper limit of normal Serum creatinine, serum phosphorous, total bilirubin, triglycerides, amylase, or lipase greater than 2.0 times the upper limit of normal Estimated glomerular filtration rate \<60mg/dl. Platelet concentration of \<100,000/ (micro)l. PT and PTT \>1.2 times the upper limit of normal for participants enrolling at the NIH Clinical Center. Hemoglobin \<10mg/dL. Positive Hepatitis B Surface Antigen and Hepatitis C Virus Antigen

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2024-01-09