HERV-K Suppression Using Antiretroviral Therapy in Volunteers With Amyotrophic Lateral Sclerosis (ALS)
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|ClinicalTrials.gov Identifier: NCT02437110|
Recruitment Status : Active, not recruiting
First Posted : May 7, 2015
Last Update Posted : January 9, 2023
- 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.
- To learn how drugs usually taken for HIV infection affect people with Amyotrophic Lateral Sclerosis (ALS).
- Adults at least 18 years old with ALS and high levels of HERV-K but no HIV.
- 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.
|Condition or disease||Intervention/treatment||Phase|
|Amyotrophic Lateral Sclerosis||Drug: Darunavir Drug: Ritonavir Drug: Dolutegravir Drug: Tenofovir alafenamide (TAF)||Phase 1|
In this Phase I, proof-of-concept study, we aim to determine whether an antiretroviral regimen approved to treat human immunodeficiency virus (HIV) infection would also suppress levels of Human Endogenous Retrovirus-K (HERV-K) found to be activated in a subset of patients with amyotrophic lateral sclerosis (ALS). We propose to measure the of blood levels of HERV-K by quantitative PCR before, during, and after treatment with an antiretroviral regimen. We will evaluate the safety of the antiretroviral regimen for participants with ALS and also explore clinical and neurophysiological outcomes of ALS symptoms, quality of life, and pulmonary function.
We will study a subset of ALS patients who have a ratio of HERV-K:RPP30 greater than or equal to 13. About 30% of ALS patients may have detectable levels of HERV-K; about 20% of patients with ALS have a level >1000 copies/ml. To show whether the HERV-K could be suppressed, we will recruit from the approximately 20% of patients with the high levels so that the antiretroviral effect can be determined.
This is an open-label study of a combination antiretroviral therapy for 24 weeks in 25 HIV-negative, HTLV-negative ALS patients with high ratio of HERV-K:RPP30. The study duration for each participant will be up to 72 weeks. Participants will be followed regularly for safety, clinical, and neurophysiological outcomes.
The primary outcome measure will be the percent decline HERV-K concentration measured by quantitataive PCR. Percent decline for a patient is measured by: 100 x (screening visit - week 24 visit measurement) / screening visit. The safety of antiretrovirals in volunteers with ALS as measured by the frequency and type of AEs, the ability to remain on assigned treatment (tolerability), physical examinations, laboratory test results, vital signs, and weight/body mass index (BMI). Efficacy will be explored by measuring the change in mean scores of: the ALS Functional Rating Scale-Revised (ALSFRS-R), the ALS Specific Quality of Life Inventory-Revised (ALSSQOL-R), the ALS Cognitive Behavioral Screen (ALS-CBS), vital capacity and maximal inspiratory pressure as measured by handheld spirometer, electrical impedance myography (EIM), the change in neurofilament levels in blood and/or CSF, and the change in uring p75ECD levels.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||122 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||HERV-K Suppression Using Antiretroviral Therapy in Volunteers With Amyotrophic Lateral Sclerosis (ALS)|
|Actual Study Start Date :||April 1, 2019|
|Actual Primary Completion Date :||November 17, 2022|
|Estimated Study Completion Date :||October 1, 2024|
20 participants with ALS and a level of HERV-K >1000 copies/ml
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.
Drug: Tenofovir alafenamide (TAF)
Orally-administered, FDA-approved medication used to treat HIV. It acts as a nucleoside reverse transcriptase inhibitor. Dose is 25mg once daily.
- The primary objective is to assess whether an antiretroviral regimen of darunavir + ritonavir, dolutegravir, and TAF for 24 weeks will suppress blood levels of HERV-K RNA below the limit of detection (1000 copies/ml) in patients with HERV-K-posi... [ Time Frame: One Year ]HERV-K Level
- The secondary objective of this study is to assess the safety of an antiretroviral regimen of darunavir + ritonavir, dolutegravir, and TAF in patients with ALS. [ Time Frame: Each study visit through week 36 ]Safety labs and assessments
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02437110
|United States, Maryland|
|National Institutes of Health Clinical Center|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Avindra Nath, M.D.||National Institute of Neurological Disorders and Stroke (NINDS)|