HERV-K Suppression Using Antiretroviral Therapy in Volunteers With Amyotrophic Lateral Sclerosis (ALS)
- 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.
|Amyotrophic Lateral Sclerosis||Drug: Darunavir Drug: Ritonavir Drug: Raltegravir Drug: Zidovudine||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||HERV-K Suppression Using Antiretroviral Therapy in Volunteers With Amyotrophic Lateral Sclerosis (ALS)|
- 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 ]
|Study Start Date:||April 23, 2015|
|Estimated Study Completion Date:||December 31, 2018|
|Estimated Primary Completion Date:||December 31, 2017 (Final data collection date for primary outcome measure)|
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 levels of plasma expression of the gag, env, and pol RNA transcripts 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 outcomes of ALS symptoms, quality of life, motor strength, and pulmonary function.
We will study a subset of ALS patients who have plasma levels of the HERV-K gag transcript > 1000 copies/ml. About 30% of ALS patients may have detectable levels of HERV-K; about 10% 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 10% 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 10 HIV-negative, HTLV-negative ALS patients with high plasma levels of HERV-K gag. 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 (<100 copies/ml) level of HERV-K gag RNA 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 gag RNA levels prior to that. Participants will be followed regularly for safety and clinical outcomes.
The primary outcome will be the proportion of participants with ALS who have undetectable (<100 copies/ml) plasma levels of HERV-K gag RNA expression as measured by quantitative PCR within 24 weeks of starting an antiretroviral regimen of darunavir + ritonavir, raltegravir, and zidovudine. The secondary objectives will be: (a) the proportion of participants with ALS who have undetectable (<100 copies/ml) plasma levels of either HERV-K pol or env RNA transcripts 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), vital capacity as measured by handheld spirometer, and quantitative muscle testing by dynamometry.
Please refer to this study by its ClinicalTrials.gov identifier: 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)|