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Protocol Details

HERV-K Suppression using Antiretroviral Therapy in Volunteers with Amyotrophic Lateral Sclerosis (ALS)

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

15-N-0126

Sponsoring Institute

National Institute of Neurological Disorders and Stroke (NINDS)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18
Max Age: N/A

Referral Letter Required

No

Population Exclusion(s)

Children

Special Instructions

Currently Not Provided

Keywords

Amyotrophic Lateral Sclerosis;
Antiretroviral Therapy;
Virus

Recruitment Keyword(s)

None

Condition(s)

Amyotrophic Lateral Sclerosis

Investigational Drug(s)

None

Investigational Device(s)

None

Intervention(s)

Drug: Darunavir
Drug: Ritonavir
Drug: dolutegravir
Drug: Tenofovir alafenamide (TAF)

Supporting Site

National Institute of Neurological Disorders and Stroke

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 study visits at Weeks 1and then every 4 weeks until Week 24. 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 36 visit, their participation is finished.

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Eligibility

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.

-Detectable HERV-K viral load in blood at a minimum of 1000 copies/ml as measured by quantitative PCR at the screening visit.

-Time from symptom onset less than 2 years.

-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 18 months.

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.

-History of having undergone gastrostomy at the time of screening.

-Participation in any other investigational drug trial or using investigational drug (within 12 weeks prior to Screening and thereafter).

-Known sulfonamide allergy.

-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 for the NIH Clinical Center.

--Serum creatinine, serum phosphorous, urine glucose, urine protein, total bilirubin, triglycerides, amylase, or lipase greater than 2.0 times the upper limit of normal for the NIH Clinical Center.

--Estimated glomerular filtration rate <60mg/dl.

--Creatine kinase greater than 3.0 times the upper limit of normal for the NIH Clinical Center.

--Platelet concentration of <100,000/ (micro)l.

--PT and PTT >1.2 times the upper limit of normal for the NIH Clinical Center.

--Hemoglobin <10mg/dL.

--Positive Hepatitis B Surface Antigen and Hepatitis C Virus Antibody


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Citations:

Andrews WD, Tuke PW, Al-Chalabi A, Gaudin P, Ijaz S, Parton MJ, Garson JA. Detection of reverse transcriptase activity in the serum of patients with motor neurone disease. J Med Virol. 2000 Aug;61(4):527-32.

Douville R, Liu J, Rothstein J, Nath A. Identification of active loci of a human endogenous retrovirus in neurons of patients with amyotrophic lateral sclerosis. Ann Neurol. 2011 Jan;69(1):141-51. doi: 10.1002/ana.22149.

Moulignier A, Moulonguet A, Pialoux G, Rozenbaum W. Reversible ALS-like disorder in HIV infection. Neurology. 2001 Sep 25;57(6):995-1001.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Avindra Nath, M.D.
National Institute of Neurological Disorders and Stroke (NINDS)
BG 10 RM 7C103
10 CENTER DR
BETHESDA MD 20814
(301) 496-1561
natha@mail.nih.gov

Amanda M. Wiebold
National Institute of Neurological Disorders and Stroke (NINDS)
National Institutes of Health
Building 10
Room 7C107
10 Center Drive
Bethesda, Maryland 20892
(301) 594-5194
amanda.wiebold@nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: 1-866-411-1010
PRPL@cc.nih.gov

Clinical Trials Number:

NCT02437110

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