HERV-K Suppression Using Antiretroviral Therapy in Volunteers With Amyotrophic Lateral Sclerosis (ALS)
Condition: Amyotrophic Lateral Sclerosis
MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis
Intervention: Darunavir; Ritonavir; Dolutegravir; Tenofovir alafenamide (TAF)
Intervention description: Orally-administered medication approved for HIV treatment. MOA is as a protease inhibitor. Dose is 600mg twice daily.; Orally-administered, FDA-approved medication for HIV treatment. Used in combination with darunavir. Dose is 100mg twice daily.; Orally-administered, FDA-approved medication to treat HIV. It acts as an integrase inhibitor. Dose is 50mg once daily.; Orally-administered, FDA-approved medication used to treat HIV. It acts as a nucleoside reverse transcriptase inhibitor. Dose is 25mg once daily.
Intervention MeSH terms: Ritonavir; Darunavir; Tenofovir; Dolutegravir
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 122.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Amyotrophic Lateral Sclerosis; Antiretroviral Therapy; Virus

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 may have a repeat lumbar puncture.

      After the Week 48 visit, their participation is finished.
    

Eligibility 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 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