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

• Status: Recruiting
• Trial end date: 2022-02-01
• Target enrollment: 0
• Participant gender: All

Summary

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 have a repeat lumbar puncture.

• After the Week 48 visit, their participation is finished.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
• Treatments: Darunavir; Dolutegravir; Raltegravir Potassium; Ritonavir; Tenofovir; Zidovudine

Criteria

• 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 criteria32 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