This study is NOT currently recruiting participants.
Number
15-N-0126
Sponsoring Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Recruitment Detail
Type: Completed Study; data analyses ongoing Gender: Male & Female Min Age: 18 Years Max Age: N/A
Referral Letter Required
No
Population Exclusion(s)
Adults who are or may become unable to consent;Pregnant Women;Children
Keywords
Amyotrophic Lateral Sclerosis; Antiretroviral Therapy; Virus
Recruitment Keyword(s)
None
Condition(s)
Amyotrophic Lateral Sclerosis
Investigational Drug(s)
Investigational Device(s)
Intervention(s)
Drug: Darunavir Drug: Ritonavir Drug: Dolutegravir Drug: Tenofovir alafenamide (TAF)
Supporting Site
National Institute of Neurological Disorders and Stroke
- 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.
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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
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
Principal Investigator
Referral Contact
For more information: