Clinical trial NCT02525471: A Pilot Study of RNS60 in Amyotrophic Lateral Sclerosis (ALS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: ALS
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2015-08-17
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety and tolerability of RNS60 in patients with Amyotrophic lateral sclerosis (ALS). Investigators will also measure the impact of RNS60 on several markers of neuro-inflammation, measured by blood biomarkers and positron emission tomography (PET) imaging.

Detailed description: Amyotrophic lateral sclerosis (ALS) is a fatal, neurodegenerative disease for which there is no cure. A substantial body of evidence implicates the neuroimmune system in ALS pathophysiology. Of relevance to this study, microglia activation in the brain has been found to correlate positively with faster rate of disease progression. In addition, studies of blood cells in people with ALS have shown an increased activation of two of the major inflammatory cell types in the body, monocytes and T cells. Among T cells, regulatory T cells (Tregs) have been recently proposed to play a role in ALS progression.

RNS60 is an electrokinetically altered aqueous fluid. Chemically, RNS60 is composed of saline and oxygen. The electrokinetic processing of RNS60 in Revalesio's patented Revalesio Pump (RP) produces charge-stabilized nanostructures (CSNs) that exhibit electrical fields. RNS60 is available for intravenous administration and inhalation. RNS60 has been extensively tested in preclinical toxicological studies and has shown very little to no side effects. In addition, RNS60 was well tolerated in three phase I human safety studies, one after intravenous administration and two after inhalation.

Preclinical in vitro and in vivo studies in multiple disease models have demonstrated that RNS60 has broad anti-inflammatory effects. These effects include reduction of microglia activation, increase of the Tregs subpopulation of lymphocytes, and neuroprotection in several disease models.

Eligibility criteria: Inclusion Criteria:

* Amyotrophic Lateral Sclerosis (ALS) volunteers must be diagnosed as having possible, probable, probable-laboratory supported, or definite ALS, either sporadic or familial according to modified El Escorial criteria.
* Age 18-80, able to provide informed consent, and comply with study procedures.
* Participants must not have taken riluzole for at least 30 days, or be on a stable dose of riluzole for at least 30 days, prior to screening (riluzole-naïve participants are permitted in the study).
* Women must not be able to become pregnant (e.g. post menopausal, surgically sterile, or using adequate birth control) for the duration of the study and 3 months after study completion.
* Males should practice contraception for the duration of the study and 3 months after completion.
* Ability to safely lie flat for 90 min for Positron Emission Tomography (PET) procedures in the opinion of the study physician.
* High or mixed affinity to bind translocator (TSPO) protein (Ala/Ala or Ala/Thr)

Exclusion Criteria:

* Abnormal liver function defined as aspartate aminotransferase (AST) and/or alanine transaminase (ALT) \> 3 times the upper limit of the normal.
* Renal insufficiency as defined by a serum creatinine \> 1.5 times the upper limit of normal.
* The presence of unstable psychiatric disease, cognitive impairment, or dementia that would impair ability of the participant to provide informed consent, according to PI judgment.
* Clinically significant unstable medical condition (other than ALS) that would pose a risk to the participant if they were to participate in the study.
* History of HIV, clinically significant chronic hepatitis, or other active infection.
* Females must not be lactating or pregnant.
* Active participation in another ALS clinical trial within 30 days of the Screening Visit
* Exposure to immunomodulatory medications within 30 days of the Screening Visit.
* Any contraindication to undergo MRI studies such as

  * History of a cardiac pacemaker or pacemaker wires
  * Metallic particles in the body
  * Vascular clips in the head
  * Prosthetic heart valves
  * Claustrophobia
* Radiation exposure that exceeds the site's current guidelines
* Current use of tobacco products including cigarettes, cigars, snuff and chewing tobacco, or nicotine replacement products such as gum or patch

Primary outcomes:
measure: Safety as Measured by the Number of Participants Experiencing Adverse Events
timeFrame: 28 weeks
measure: Tolerability to Complete the Entire 24 Week Study on Study Drug
timeFrame: 24 weeks
measure: Blood Biomarkers of Inflammation.
timeFrame: 24 Weeks
measure: Change From Baseline in Standardized Uptake Value (SUV) Normalized to Whole Brain Mean (SUVR) at Approximately 60-90 Minutes Post Injection
timeFrame: 24 Weeks
measure: Clinical Outcome: Change in Pulmonary Function From Baseline to Week 23, Measured by Slow Vital Capacity (SVC)
timeFrame: 24 Weeks
measure: Clinical Outcome: Change in Strength From Baseline to Week 23, Measured by Accurate Test of Limb Isometric Strength (ATLIS)
timeFrame: 24 Weeks
measure: Clinical Outcome: Change in Functional Status Between Baseline and Week 23, Measured by Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)
timeFrame: 24 Weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Sabrina Paganoni, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital
name: Nazem Atassi, MD
role: PRINCIPAL_INVESTIGATOR
References: