HERV-K Suppression Using Antiretroviral Therapy in Volunteers With Amyotrophic Lateral Sclerosis (ALS)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02437110|
Recruitment Status : Enrolling by invitation
First Posted : May 7, 2015
Last Update Posted : September 13, 2018
- 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.
- Participants will be screened with medical history, physical exam, and blood and breathing tests.
- Visit 2: participants will have medical history, questionnaires, and blood drawn. Their strength will be tested by pushing on a machine. They will blow into a tube that measures the air they can hold in their lungs.
- After Visit 2, participants will start taking the 4 study drugs twice a day.
- Participants will have study visits at Weeks 1, 2, and 4, then every 4 weeks until Week 36. They will be asked how they are feeling and have an exam and blood drawn. At 2 visits, they will have tests of strength, breathing, and their ALS symptoms. Some visits may be done at their ALS doctor s office.
- At Week 24, they will stop taking the study drugs.
- After the Week 36 visit, their participation is finished.
|Condition or disease||Intervention/treatment||Phase|
|Amyotrophic Lateral Sclerosis||Drug: Darunavir Drug: Ritonavir Drug: Raltegravir Drug: Zidovudine||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 blood levels of the HERV-K transcript > 1000 copies/ml. 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 up to 24 weeks in 20 HIV-negative, HTLV-negative ALS patients with high blood levels of HERV-K . The study duration for each participant will be approximately 44 weeks with an 8-week screening window, 24-week treatment phase, and 12-week follow-up phase. If participants have an undetectable (<1000 copies/ml) level of HERV-K viral load at two consecutive study visits before the end of the 24-week treatment phase, the study drugs will be discontinued as the primary outcome will have been satisfied at that point. Participants will stay on the antiretroviral regimen for at least 8 weeks regardless of if they have undetectable HERV-K viral load levels prior to that. Participants will be followed regularly for safety, clinical, and neurophysiological outcomes.
The primary outcome will be the proportion of participants with ALS who have undetectable (<1000 copies/ml) blood levels of HERV-K viral load as measured by quantitative PCR within 24 weeks of starting an antiretroviral regimen of darunavir + ritonavir, dolutegravir, and tenofovir alafenamide fumerate (TAF). The secondary objectives will be: (a) the proportion of participants with ALS who have undetectable (<1000 copies/ml) blood levels of HERV-K viral load within 24 weeks of starting the antiretroviral regimen; and (b) the safety of antiretrovirals in volunteers with ALS as measured by the frequency and type of adverse events (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 as measured by handheld spirometer, neurophysiological measures, and the change in neurofilament levels in blood and/or CSF.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 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)|
|Study Start Date :||April 23, 2015|
|Estimated Primary Completion Date :||December 31, 2018|
|Estimated Study Completion Date :||December 31, 2018|
- Drug: Darunavir
Orally-administered medication approved for HIV treatment. MOA is as a protease inhibitor. Dose is 600mg twice daily.
- Drug: Ritonavir
Orally-administered, FDA-approved medication for HIV treatment. Used in combination with darunavir. Dose is 100 mg twice daily.
- Drug: Raltegravir
Orally-administered, FDA-approved medication to treat HIV. It acts as an integrase inhibitor. Dose is 400mg twice daily.
- Drug: Zidovudine
Orally-administered, FDA-approved medication used to treat HIV. It acts as a nucleoside reverse transcriptase inhibitor. Dose is 300mg twice daily.
- The proportion of participants with an undetectable HERV-K gag RNA level by quantitative PCR within 24 weeks of starting an antiretroviral regimen of darunavir, ritonavir, raltegravir, and zidovudine [ Time Frame: 24 weeks ]
- Safety and feasibility of up to 24 weeks of darunavir, ritonavir, raltegravir, and zidovudine for patients with ALS [ Time Frame: 24 weeks ]
- The proportion of participants with an undetectable HERV-K env or pol RNA level by quantitative PCR within 24 weeks of starting an antiretroviral regimen of darunavir, ritonavir, raltegravir, and zidovudine [ Time Frame: 24 weeks ]
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, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Avindra Nath, M.D.||National Institute of Neurological Disorders and Stroke (NINDS)|