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

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 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