HERV-K Suppression Using Antiretroviral Therapy in Volunteers With Amyotrophic Lateral Sclerosis (ALS)
Study Purpose:
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).
Disease:
Amyotrophic Lateral Sclerosis (ALS), Familial ALS, Sporadic ALSStudy Type:
Interventional TrialStudy Category:
Drug TrialStudy Status:
EnrollingPhase:
Phase IStudy Chair(s)/Principal Investigator(s):
Avindra Nath, M.D. National Institute of Neurological Disorders and Stroke (NINDS)
Clinicaltrials.gov ID (11 digit #):
NCT02437110Neals Affiliated?
NoCoordinating Center Contact Information
National Institute of Neurological Disorders and Stroke (NINDS)Avindra Nath, M.D. / .(JavaScript must be enabled to view this email address) / 301-496-1561
Amanda M Wiebold / .(JavaScript must be enabled to view this email address) / 301-594-5194
Bethesda, Maryland 20814 United States
Full Study Summary:
Objective:
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.
Study Population:
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.
Design:
This is an open-label study of a combination antiretroviral therapy for 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 up to 60 weeks. Participants will be followed regularly for safety, clinical, and neurophysiological outcomes.
Outcome Measures:
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 as measured by handheld spirometer, electrical impedance myography (EIM), the change in neurofilament levels in blood and/or CSF, and the chanage in uring p75ECD levels.