Parkinson's DiseasePhase 2REPAIR-PDNCT03815916
31P-MRS Imaging to Assess the Effects of CNM-Au8 on Impaired Neuronal Redox State in Parkinson's Disease
A Phase 2 study testing Gold Nanocrystals in people with Parkinson's Disease, run by Clene Nanomedicine at 1 site in United States.
Trial summary
REPAIR-PD is a single-center open label pilot, sequential group, investigator and patient blinded study to assess the CNS metabolic effects, safety, pharmacokinetics, and pharmacodynamics of CNM-Au8 in patients who have been diagnosed with Parkinson's Disease (PD) within three (3) years of Screening. Read more about this study
- Who is it for?
- Ages 30 to 80 years
- Conditions the study is for
- Parkinson's Disease
- What is being tested?
- Gold Nanocrystals
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Dec 2019to 7 Jun 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Able to understand and give written informed consent and follow study procedures.
- Male or female, aged 30 - 80 years or age (inclusive) at the time of PD diagnosis.
- PD subjects will be recruited in accordance with the MDS Clinical Diagnostic Criteria for
- PD:
- Parkinsonism present (bradykinesia + either rest tremor or rigidity)
- 2 of the following 4 supportive criteria:
Show all 13Show fewer
- Clear and dramatic beneficial response to dopaminergic medication
- Presence of levodopa-induced dyskinesias
- Rest tremor of a limb
- Olfactory loss or cardiac sympathetic denervation seen on prior MIBG SPECT
- Duration of PD since diagnosis is </= 3 years (inclusive)
- Modified Hoehn and Yahr stage </= 3
- Treatment with dopaminergic therapy for at least 12-weeks and with no change in current medications within the prior 6-weeks
Who cannot join
- Atypical parkinsonism, including that due to drugs, metabolic disorders, encephalitis, cerebrovascular disease, normal pressure hydrocephalus, or other neurodegenerative disease.
- The presence of any of the following:
- Unequivocal cerebellar abnormalities
- Downward vertical gaze limitation or slowing of downward saccades
- Diagnosis of behavioral variant frontotemporal dementia or primary progressive aphasia
- Parkinsonian features restricted to the lower limbs for > 3 years
Show all 33Show fewer
- Treatment with dopamine blockers or depleters in a time course consistent with drug-induced parkinsonism
- Absence of an observable response to high dose levodopa despite moderate disease severity
- Expert considers a diagnosis of alternative syndrome more likely than PD
- Rapid progression of gait impairment requiring wheelchair within 5 years of onset
- Complete absence of progression of motor symptoms over 3 years unless due to treatment
- Early bulbar dysfunction within the first 5 years since diagnosis
- Inspiratory respiratory dysfunction (stridor or frequent sighs)
- Severe autonomic failure in the first 5 years
- Recurrent falls (>1 per year) because of impaired balance in the first 3 years
- Disproportionate dystonic anterocollis or hand contractures of hands or feet within 10 years
- Absence of any of the common non-motor features of PD despite 5 years of disease
- Otherwise unexplained pyramidal tract signs (weakness, hyperreflexia, or extensor toe signs)
- Bilateral symmetric parkinsonism
- Mini-Mental State Exammination (MMSE) score of less than 19.
- Patient with a history of any clinically significant or unstable medical condition based on the Investigator's judgment.
- History of human immunodeficiency virus (HIV), hepatitis C (HepC) virus antibody, or hepatitis B (HepB) virus antibody.
- 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 may interfere with study participation.
- Patients with clinically significant hepatic or renal dysfunction or clinical laboratory findings that would limit the interpretability of change in liver or kidney function, or those with low platelet counts (<150 x 109 per liter) or eosinophilia (absolute eosinophil count of ≥500 eosinophils per microliter) at Screening.
- Patient participating in any other investigational drug trial or using investigational drug (within 12 weeks prior to screening and thereafter)
- Positive screen for drugs of abuse or known history of alcohol abuse.
- Women of child-bearing potential, or men, who are unwilling or unable to use accepted methods of birth control for up to 6 months following study participation.
- Women with a positive pregnancy test, are lactating, or are planning to become pregnant during the study or within 6 months of the end of this trial.
- 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.
- History of allergy to gold in any form.
- Patient is considered a suicide risk in the opinion of the Investigator, has previously made a suicide attempt, or is currently demonstrating active suicidal ideation. Subjects with intermittent passive suicidal ideation are not necessarily excluded based on the assessment of the Investigator.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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 Parkinson's Disease
REPAIR-PD is a single-center open label pilot, sequential group, investigator and patient blinded study to assess the CNS metabolic effects, safety, pharmacokinetics, and pharmacodynamics of CNM-Au8 in patients who have been diagnosed with Parkinson's Disease (PD) within three (3) years of Screening. The primary endpoint is the ratio of the oxidized to reduced form of nicotinamide adenine dinucleotide (NAD+:NADH) measured non-invasively by 31phosphorous magnetic resonance spectroscopy (31P-MRS).
Read the 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 Parkinson's Disease within three years 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=15 patients/cohort, total n=30 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 six-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.
- Conditions
- Parkinson's Disease
- Being tested
- Gold Nanocrystals
- Keywords
- neurodegeneration, gold, nanocrystal, NAD+, redox, 31P-MRS, Parkinson's Disease, magnetic resonance spectroscopy, nanoparticle, nanomedicine, NADH
- Medical subject headings
- Parkinson Disease, Nerve Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gold NanocrystalsDrug
Also called CNM-Au8
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.
| Study group | Role | What they receive |
|---|---|---|
| 7.5mg CNM-Au8 | Experimental | 7.5mg suspension of clean-surfaced, faceted, gold nanocrystals in 120ml of sodium bicarbonate buffered water Receives: Drug: Gold Nanocrystals |
| 15mg CNM-Au8 | Experimental | 15mg suspension of clean-surfaced, faceted, gold nanocrystals in 120ml of sodium bicarbonate buffered water Receives: Drug: Gold Nanocrystals |
| 30mg CNM-Au8 | Experimental | 30mg suspension of clean-surfaced, faceted, gold nanocrystals in 120ml of sodium bicarbonate buffered water Receives: Drug: Gold Nanocrystals |
| 60mg CNM-Au8 | Experimental | 60mg suspension of clean-surfaced, faceted, gold nanocrystals in 120ml of sodium bicarbonate buffered water Receives: Drug: Gold Nanocrystals |
What is being measured
The primary outcome is the main question the study is designed to answer.
31P-MRS Redox Ratio
The change in 31P-MRS NAD+/NADH ratio was measured by a partial volume coil that images the parietal and occipital lobes as a single value with respect to the fraction (%) of the nicotinamide adenine dinucleotide (NAD) signal measured as either the oxidized (NAD+) or reduced form (NADH).
The primary endpoint was the mean change from Baseline to Week 12 in the ratio of NAD+ to NADH (NAD+/NADH) in the Intent to Treat population. A paired t-test was used to analyze the mean change from baseline.
Measured: Baseline to 12 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2019
- Study start19 Dec 2019
- Primary completion7 Jun 2021
- Study completion7 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Open Label, Investigator Blinded, Sequential Cohort (max of 2 cohorts amongst the possible 4 interventions)
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Clene Nanomedicine
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University of Texas Southwestern Medical Center
- Responsible party
- Sponsor
- Investigators
- Richard Dewey, MD, Principal investigator, UT Southwestern
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03815916
- Sponsor's protocol ID
- CNMAu8.202
- Acronym
- REPAIR-PD
- Status last verified
- May 2024
- First submitted
- 18 Jan 2019
- Last updated
- 16 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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 Parkinson's Disease
- ClinicalTrials.gov ID
- NCT03815916
- Acronym / sponsor ID
- REPAIR-PD / CNMAu8.202
- Conditions
- Parkinson's Disease
- Keywords
- neurodegeneration, gold, nanocrystal, NAD+, redox, 31P-MRS, Parkinson's Disease, magnetic resonance spectroscopy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Clene NanomedicineIndustry (pharma, biotech, devices)
- Collaborators
- University of Texas Southwestern Medical Center
- Study start
- 19 Dec 2019 (actual)
- Primary completion
- 7 Jun 2021 (actual)
- Study completion
- 7 Jun 2021 (actual)
- First posted
- 24 Jan 2019 (actual)
- Results
- Posted 16 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
REPAIR-PD is a single-center open label pilot, sequential group, investigator and patient blinded study to assess the CNS metabolic effects, safety, pharmacokinetics, and pharmacodynamics of CNM-Au8 in patients who have been diagnosed with Parkinson's Disease (PD) within three (3) years of Screening. The primary endpoint is the ratio of the oxidized to reduced form of nicotinamide adenine dinucleotide (NAD+:NADH) measured non-invasively by 31phosphorous magnetic resonance spectroscopy (31P-MRS).
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 Parkinson's Disease within three years 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=15 patients/cohort, total n=30 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 six-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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Open Label, Investigator Blinded, Sequential Cohort (max of 2 cohorts amongst the possible 4 interventions)
| Arm | Type | Receives |
|---|---|---|
| 7.5mg CNM-Au8 | Experimental | Drug: Gold Nanocrystals7.5mg suspension of clean-surfaced, faceted, gold nanocrystals in 120ml of sodium bicarbonate buffered water |
| 15mg CNM-Au8 | Experimental | Drug: Gold Nanocrystals15mg suspension of clean-surfaced, faceted, gold nanocrystals in 120ml of sodium bicarbonate buffered water |
| 30mg CNM-Au8 | Experimental | Drug: Gold Nanocrystals30mg suspension of clean-surfaced, faceted, gold nanocrystals in 120ml of sodium bicarbonate buffered water |
| 60mg CNM-Au8 | Experimental | Drug: Gold Nanocrystals60mg suspension of clean-surfaced, faceted, gold nanocrystals in 120ml of sodium bicarbonate buffered water |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Able to understand and give written informed consent and follow study procedures.
- Male or female, aged 30 - 80 years or age (inclusive) at the time of PD diagnosis.
- PD subjects will be recruited in accordance with the MDS Clinical Diagnostic Criteria for
- Duration of PD since diagnosis is </= 3 years (inclusive)
- Modified Hoehn and Yahr stage </= 3
Key exclusion criteria (33 listed)
- Atypical parkinsonism, including that due to drugs, metabolic disorders, encephalitis, cerebrovascular disease, normal pressure hydrocephalus, or other neurodegenerative disease.
- The presence of any of the following:
- Mini-Mental State Exammination (MMSE) score of less than 19.
- Patient with a history of any clinically significant or unstable medical condition based on the Investigator's judgment.
- History of human immunodeficiency virus (HIV), hepatitis C (HepC) virus antibody, or hepatitis B (HepB) virus antibody.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Gold NanocrystalsAlso: CNM-Au8CNM-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. | Drug | 15mg CNM-Au8, 30mg CNM-Au8, 60mg CNM-Au8, 7.5mg CNM-Au8 |
Primary outcome
31P-MRS Redox Ratio
Time frame: Baseline to 12 Weeks
The change in 31P-MRS NAD+/NADH ratio was measured by a partial volume coil that images the parietal and occipital lobes as a single value with respect to the fraction (%) of the nicotinamide adenine dinucleotide (NAD) signal measured as either the oxidized (NAD+) or reduced form (NADH). The primary endpoint was the mean change from Baseline to Week 12 in the ratio of NAD+ to NADH (NAD+/NADH) in the Intent to Treat population. A paired t-test was used to analyze the mean change from baseline.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Parkinson's Disease
Enrolling by invitationObservational study
Early Molecular Biomarkers for Differentiating Parkinsonian Syndromes
PARKINSON DISEASE (Disorder), Atypical Parkinsonism
Active, not recruitingPhase 1/2
Clinical Safety and Efficacy of Umbilical Cord Mesenchymal Stromal Cells-derived Exosomes in Patients With Parkinson's Disease
Parkinson Disease (PD)
Active, not recruitingObservational study
Adaptive DBS to Offset STN Dysregulation During Exercise in PD
Parkinson Disease
Not yet recruiting
Compulsive Eating and Brain's Reward System in Different Pathologies
PARKINSON DISEASE (Disorder), Bipolar 1 Disorder
Not yet recruiting
Evaluating the Effect of the Zeen Mobility Device on Clinical Practicality, Safety, and Impact (Via Assessments of Walking, Standing Tolerance, Balance, Endurance, Effort, and Participation in Daily Tasks) in an Outpatient Rehabilitation Setting for Individuals With Mobility Impairments.
Stroke, Parkinson's Disease (PD)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard Dewey, MD principal investigator
UT Southwestern
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Gold Nanocrystals in people with Parkinson's Disease, run by Clene Nanomedicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
31P-MRS Redox Ratio (time frame: Baseline to 12 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2024.