- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03843710
31P-MRS Imaging to Assess the Effects of CNM-Au8 on Impaired Neuronal Redox State in Amyotrophic Lateral Sclerosis (REPAIR-ALS) (REPAIR-ALS)
A Phase 2, Pilot Open Label, Sequential Group, Investigator Blinded Study of Magnetic Resonance Spectroscopy (31P-MRS) to Assess the Effects of CNM-Au8 for the Bioenergetic Improvement of Impaired Neuronal Redox State in Amyotrophic Lateral Sclerosis
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a single-center open label pilot, sequential group, investigator blinded study of the CNS metabolic effects, safety, pharmacokinetics, and pharmacodynamics of CNM-Au8 in patients who have been diagnosed with Amyotrophic Lateral Sclerosis within twelve months of Screening. The Sponsor will select a starting treatment dose of CNM-Au8 for the initial treatment. Investigators and patients will be blinded to each cohort's study dose. Upon completion of the first treatment cohort, the Sponsor will select a single dose or two different doses for the subsequent second cohort from a pre-specified dosing selection plan based on the evaluation of the 31P-Magnetic Resonance Spectroscopy (31P-MRS) changes versus baseline in the first cohort. Up to a total of two treatment cohorts may be studied (n=12 patients/cohort, total n=24 patients). All patients will receive daily oral treatment over twelve consecutive weeks during each cohort's Treatment Period.
There will be three study periods per treatment cohort:
A four-week screening period (Screening Period); A twelve-week treatment period (Treatment Period); A four-week follow-up period (End-of-Study Assessment).
The primary study outcome, CNS metabolic changes, will be assessed based upon each patient's Week 12 study visit versus the pre-treatment baseline. The primary endpoint is the brain metabolic effects of treatment with CNM-Au8 as assessed by an improvement of 31P-MRS assessment of Brain Tissue Cellular Redox Potential defined by the measured tissue ratio of NAD+:NADH concentrations following 12 weeks of once daily treatment.
Study Type
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Texas
-
Dallas, Texas, United States, 75390
- UT Southwestern
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Able to understand and give written informed consent.
- Male or female patients aged 35 years or greater (inclusive) and less than 75 years of age at the time of ALS diagnosis.
- Patients with a confirmed ALS diagnosis: "definite ALS" or "probable ALS" or "possible" diagnostic criteria per the revised El Escorial Criteria as determined by a neurologist subspecializing in ALS (e.g., the Principal Investigator by study site).
- Stable background therapy (e.g., stable dosing of riluzole within the prior 6-weeks) per Investigator discretion.
- At the time of Screening disease duration less than or equal to 24-months from symptom onset OR within 12-moths of a confirmed ALS diagnosis.
- Forced vital capacity (FVC) >/= 60% of predicted value as adjusted for gender, height, and age at the Screening Visit.
- Patients who are ambulatory (e.g., normal ambulation, early ambulation difficulties, or walks with assistance) on the ALSFRS-R scale.
Exclusion Criteria:
At Screening patients who utilize, or in the Investigator's judgment will be imminently dependent upon during the course of this study:
- Non-invasive ventilation
- Gastrostomy (e.g., use of percutaneous endoscopic gastrostomy tube)
- Use of wheel chair
- Patient who have previously undergone tracheostomy.
- Patient with a history of significant other major medical condition based on the Investigator's judgment.
- Based on the investigator's judgment, patients who may have difficulty complying with the protocol and/or study procedures.
- Patient with clinically significant abnormalities in hematology, blood chemistry, ECG, or physical examination not resolved by the Baseline visit which according to Investigator can interfere with study participation.
- Patient participating in any other investigational drug trial or using investigational drug (within 12 weeks prior to screening and thereafter)
- Females who are pregnant or nursing or who plan to get pregnant during the course of this clinical trial or within 6 months of the end of this trial.
- Positive screen for drugs of abuse or known alcohol abuse.
- Women of child-bearing potential, or men, who are unwilling or unable to use accepted methods of birth control during the study or for 6 months following completion of study participation.
- Women with a positive pregnancy test, are lactating, or are planning to become pregnant during the study.
- Patients with implanted metal objects in their body that may be affected by an MRI procedure.
- Patients who are claustrophobic or otherwise unlikely to be able to complete the MRI scanning procedures.
- Patients with a history of gold allergy.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 7.5mg CNM-Au8
7.5mg suspension of clean-surfaced, faceted, gold nanocrystals in 120ml of sodium bicarbonate buffered water
|
CNM-Au8 is a dark red/purple-colored liquid formulation consisting of a stable suspension of faceted clean surfaced elemental gold nanocrystals in buffered deionized water with a concentration of up to 0.5 mg/mL of gold.
The formulation is buffered by sodium bicarbonate present at a concentration of 0.546 mg/mL.
There are no other excipients.
The drug product is formulated to be taken orally and will be provided in single dose HDPE containers.
The study doses vary by the concentration of gold nanocrystals per milliliter in a volume of 60 mL.
Other Names:
|
Experimental: 15mg CNM-Au8
15mg suspension of clean-surfaced, faceted, gold nanocrystals in 120ml of sodium bicarbonate buffered water
|
CNM-Au8 is a dark red/purple-colored liquid formulation consisting of a stable suspension of faceted clean surfaced elemental gold nanocrystals in buffered deionized water with a concentration of up to 0.5 mg/mL of gold.
The formulation is buffered by sodium bicarbonate present at a concentration of 0.546 mg/mL.
There are no other excipients.
The drug product is formulated to be taken orally and will be provided in single dose HDPE containers.
The study doses vary by the concentration of gold nanocrystals per milliliter in a volume of 60 mL.
Other Names:
|
Experimental: 30mg CNM-Au8
30mg suspension of clean-surfaced, faceted, gold nanocrystals in 120ml of sodium bicarbonate buffered water
|
CNM-Au8 is a dark red/purple-colored liquid formulation consisting of a stable suspension of faceted clean surfaced elemental gold nanocrystals in buffered deionized water with a concentration of up to 0.5 mg/mL of gold.
The formulation is buffered by sodium bicarbonate present at a concentration of 0.546 mg/mL.
There are no other excipients.
The drug product is formulated to be taken orally and will be provided in single dose HDPE containers.
The study doses vary by the concentration of gold nanocrystals per milliliter in a volume of 60 mL.
Other Names:
|
Experimental: 60mg CNM-Au8
60mg suspension of clean-surfaced, faceted, gold nanocrystals in 120ml of sodium bicarbonate buffered water
|
CNM-Au8 is a dark red/purple-colored liquid formulation consisting of a stable suspension of faceted clean surfaced elemental gold nanocrystals in buffered deionized water with a concentration of up to 0.5 mg/mL of gold.
The formulation is buffered by sodium bicarbonate present at a concentration of 0.546 mg/mL.
There are no other excipients.
The drug product is formulated to be taken orally and will be provided in single dose HDPE containers.
The study doses vary by the concentration of gold nanocrystals per milliliter in a volume of 60 mL.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in 31P-MRS Redox Ratio (NAD+/NADH)
Time Frame: At 12 Weeks
|
Mean change in average NAD+/NADH measured brain Redox Ratio by treatment group
|
At 12 Weeks
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mean Change in 31P-MRS Membrane Component Tissue Concentration of Phosphoethanolamine (PE)
Time Frame: At 12 Weeks
|
Mean change in average CNS concentration of PE [mmol/kg] by treatment group
|
At 12 Weeks
|
Mean Change in 31P-MRS Membrane Component CNS Tissue Concentration of Phosphocholine (PC)
Time Frame: At 12 Weeks
|
Mean change in average CNS concentration of PC [mmol/kg] by treatment group
|
At 12 Weeks
|
Mean Change in 31P-MRS Membrane Component CNS Tissue Concentration of Glycerophosphocholine (GPC)
Time Frame: At 12 Weeks
|
Mean change in average CNS concentration of GPC [mmol/kg] by treatment group
|
At 12 Weeks
|
Mean Change in 31P-MRS Bioenergetic Metabolite CNS Tissue Concentration of NAD+
Time Frame: At 12 Weeks
|
Mean change in average CNS concentration of NAD+ [mmol/kg] by treatment group
|
At 12 Weeks
|
Mean Change in 31P-MRS Bioenergetic Metabolite CNS Tissue Concentration of NADH
Time Frame: At 12 Weeks
|
Mean change in average CNS concentration of NADH [mmol/kg] by treatment group
|
At 12 Weeks
|
Mean Change in 31P-MRS Bioenergetic Metabolite CNS Tissue Concentration of ATP
Time Frame: At 12 Weeks
|
Mean change in average CNS concentration of ATP [mmol/kg] (as internal reference) by treatment group
|
At 12 Weeks
|
Mean Change in 31P-MRS Bioenergetic Metabolite CNS Tissue Concentration of Phosphocreatine (PCr)
Time Frame: At 12 Weeks
|
Mean change in average CNS concentration of PCr [mmol/kg] by treatment group
|
At 12 Weeks
|
Mean Change in 31P-MRS Bioenergetic Metabolite CNS Tissue Concentration of Intracellular Inorganic Phosphate (Pi(in))
Time Frame: At 12 Weeks
|
Mean change in average CNS concentration of Pi(in) [mmol/kg] by treatment group
|
At 12 Weeks
|
Mean Change in 31P-MRS Bioenergetic Metabolite CNS Tissue Concentration of Extracellular Inorganic Phosphate (Pi(ex))
Time Frame: At 12 Weeks
|
Mean change in average CNS concentration of Pi(ex) [mmol/kg] by treatment group
|
At 12 Weeks
|
Mean Change in 31P-MRS Bioenergetic Metabolite CNS Tissue Concentration of Uridine Diphosphate Glucose (UDPG)
Time Frame: At 12 Weeks
|
Mean change in average CNS concentration of UDPG [mmol/kg] by treatment group
|
At 12 Weeks
|
Mean Change in 31P-MRS Membrane Component CNS Tissue Concentration of Glycerophosphoethanolamine (GPE)
Time Frame: At 12 Weeks
|
Mean change in average CNS concentration of GPE [mmol/kg] by treatment group
|
At 12 Weeks
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Jeffery Elliott, MD, UT Southwestern
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CNMAu8.203
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Amyotrophic Lateral Sclerosis
-
Washington University School of MedicineMassachusetts General HospitalSuspendedAmyotrophic Lateral Sclerosis, Familial | Amyotrophic Lateral Sclerosis, SporadicUnited States
-
University of Sao Paulo General HospitalPontifícia Universidade Católica do ParanáUnknownAMYOTROPHIC LATERAL SCLEROSISBrazil
-
Neuromed IRCCSRecruitingAmyotrophic Lateral Sclerosis (ALS)Italy
-
Humanitas Mirasole SpAKU Leuven; UMC Utrecht; University of Sheffield; Istituto Superiore di Sanità; University... and other collaboratorsActive, not recruitingAmyotrophic Lateral Sclerosis (ALS)United Kingdom, Germany, France, Netherlands, Belgium, Ireland, Italy
-
The Methodist Hospital Research InstituteMassachusetts General Hospital; The Center for Clinical and Translational Sciences... and other collaboratorsActive, not recruiting
-
CytokineticsCompletedAmyotrophic Lateral Sclerosis (ALS)United States, Netherlands, Canada, Belgium, United Kingdom, France, Germany, Ireland, Italy, Portugal, Spain
-
Columbia UniversityALS AssociationTerminatedAmyotrophic Lateral Sclerosis (ALS)United States
-
El Instituto Nacional de Neurologia y Neurocirugia...CompletedAmyotrophic Lateral Sclerosis | Amyotrophic Lateral Sclerosis, SporadicMexico
-
University Hospital, GenevaCompletedAmyotrophic Lateral Sclerosis 11Switzerland
-
Fondazione Don Carlo Gnocchi OnlusFondazione Salvatore MaugeriCompleted
Clinical Trials on Gold Nanocrystals
-
Clene NanomedicineUniversity of Texas Southwestern Medical CenterRecruitingMultiple SclerosisUnited States
-
Clene NanomedicineUniversity of Texas Southwestern Medical CenterCompletedParkinson's DiseaseUnited States
-
Clene NanomedicineCompletedHealthy Volunteers - Male and FemaleNetherlands
-
NestléCompletedStool CompositionPhilippines
-
4Life Research, LLCSt. Louis University; Professional Athletic OrthopedicsCompletedRheumatoid Arthritis | Knee Osteoarthritis | Knee Arthritis | Knee Discomfort | Knee Pain Chronic | Knee Pain SwellingUnited States
-
Gitte Fredberg PerssonCompleted
-
Sten Rasmussen, MD, PhDAalborg UniversityCompleted
-
Ahram Canadian UniversityCompleted
-
Northern Orthopaedic Division, DenmarkAarhus University Hospital; University of AarhusWithdrawn
-
Tongji HospitalShanghai Zhongshan Hospital; Peking University Third Hospital; Huashan Hospital; First Affiliated Hospital Xi'an Jiaotong University and other collaboratorsCompleted