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

NCT02437110 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 15012615-N-0126
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Amyotrophic Lateral Sclerosis; Antiretroviral Therapy; Virus

Outcome Measures

Primary Outcomes (1)

• Percent Change in HERV-K Level

  Blood samples were obtained during the screening visit and week 24 (post-treatment with antiretroviral drugs). The percent change in HERV-K level was measured using quantitative PCR: 100% x (screening visit - week 24 visit measurement) / screening visit.

  24 weeks

Study Arms (1)

ALS

EXPERIMENTAL

20 participants with ALS and a level of HERV-K:RPP30 greater than or equal to 13

Drug: Darunavir; Drug: Ritonavir; Drug: Dolutegravir; Drug: Tenofovir alafenamide (TAF)

Interventions

Darunavir DRUG

Orally-administered medication approved for HIV treatment. MOA is as a protease inhibitor. Dose is 600mg twice daily.

ALS

Ritonavir DRUG

Orally-administered, FDA-approved medication for HIV treatment. Used in combination with darunavir. Dose is 100mg twice daily.

ALS

Dolutegravir DRUG

Orally-administered, FDA-approved medication to treat HIV. It acts as an integrase inhibitor. Dose is 50mg once daily.

ALS

Tenofovir alafenamide (TAF) DRUG

Orally-administered, FDA-approved medication used to treat HIV. It acts as a nucleoside reverse transcriptase inhibitor. Dose is 25mg once daily.

ALS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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. doi: 10.1002/1096-9071(200008)61:43.0.co;2-a.

  PMID: 10897073 BACKGROUND

• 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.

  PMID: 21280084 BACKGROUND

• Moulignier A, Moulonguet A, Pialoux G, Rozenbaum W. Reversible ALS-like disorder in HIV infection. Neurology. 2001 Sep 25;57(6):995-1001. doi: 10.1212/wnl.57.6.995.

  PMID: 11571323 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Virus Diseases

Interventions

Darunavir; Ritonavir; dolutegravir; tenofovir alafenamide

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Infections

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Azoles

Results Point of Contact

• Title: Dr. Avi Nath
• Organization: National Institutes of Health

natha@mail.nih.gov

301-496-1561

Study Officials

• Avindra Nath, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2015
• First Posted: May 7, 2015
• Study Start: April 1, 2019
• Primary Completion: November 17, 2022
• Study Completion: May 9, 2023
• Last Updated: January 9, 2024
• Results First Posted: January 9, 2024

Record last verified: 2022-12

Locations

US (1)