Mild Cognitive Impairment
Conditions
Keywords
Mild Cognitive Impairment
Brief summary
To investigate whether \[18F\]NAV4694 positron emission tomography (PET) scan findings have the ability to distinguish subjects with mild cognitive impairment (MCI) who progress to Alzheimer's disease (AD) from those who do not.
Interventions
DRUG[18F]NAV4694
Sponsors
Navidea Biopharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Subject has signed informed consent to participate in the study and continues to give willing consent for participation * Age ≥ 55 years with a diagnosis of MCI * Educational level of at least 6 years * Female subjects will not be of child-bearing potential (\> 1 year post-menopausal or surgically sterile) * Availability of a study partner who can assist in completing rating scales for the duration of the study * Cognitive complaints reported by the subject and confirmed by the study partner * Clinical Dementia Rating (CDR) global score = 0.5 * Mini-mental state examination (MMSE) score of 24-30 * Diagnostic and Statistical Manual of Mental Disorders, Version 4, Text Revised (DSM-IV-TR) criteria of dementia not fulfilled
Exclusion criteria
* Has been previously enrolled in this study and received the investigational product * Has received an investigational product within 30 days prior to screening * Has received disease-modifying therapy that could have changed amyloid brain deposition * Has exceeded yearly radioactive dose of 30 mSv * Has a known allergy to the study drug or any of its constituents * Has a history of alcohol abuse or alcohol dependency in the 3 years prior to study entry, or is an alcoholic or drug addict, as determined by the investigator * Has ongoing clinically significant (as judged by the investigator), metabolic or any other disease that could currently cause impaired memory (e.g., untreated thyroid disease, vitamin or other nutritional deficiencies, chronic kidney, or liver disease) * Memory impairment that can be attributed to a disease or condition other than an early phase neurodegenerative syndrome * Has a parkinsonian movement disorder * Use of psychoactive medications that would affect the subject's ability to reliably perform neurocognitive testing or create uncertainty in distinguishing between the effects of the psychoactive medication and the subject's underlying cognitive impairment (e.g., benzodiazepines, sedatives, antipsychotics) * Has received any contrast material (X-ray, MRI) or radiopharmaceutical within 48 hours prior to, or a therapeutic radiopharmaceutical (e.g., 131I) within 10 days prior to, or any radiopharmaceutical administration within 10 radioactive half-lives prior to the administration of the investigational product or for whom administration of such substances is planned within 7 days after investigational product administration * History of major recurrent depressive disorder (per DSM-IV-TR) within the last 5 years prior to screening * Has a brain tumor or other intracranial lesion, a disturbance of cerebral spinal fluid circulation (e.g., normal pressure hydrocephalus), and/or a significant history of head trauma or brain surgery * Has signs of major cerebrovascular disease, as verified by medical history and/or brain MRI * Is scheduled for surgery and/or another invasive procedure within the 7 days following investigational product administration * Has any contraindication to MRI examination, e.g., metal implants, phobia, or cannot undergo an MRI for other reasons such as the inability to lie flat
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Mild Cognitive Impairment Progression to Alzheimer's Disease | 3 Years | Incidence of Mild Cognitive Impairment Progression to Alzheimer's Disease |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Neuro-cognitive Test Battery Scores at 6 Months Compared to Baseline | 6 months | Change in Neuro-cognitive Test Battery Scores at 6 months compared to baseline |
| Change in Neuro-cognitive Test Battery Scores at 12 Months Compared to Baseline | 12 months | Change in Neuro-cognitive Test Battery Scores at 12 months compared to baseline |
| Change in Neuro-cognitive Test Battery Scores at 18 Months Compared to Baseline | 18 months | Change in Neuro-cognitive Test Battery Scores at 18 months compared to baseline |
| Change in Neuro-cognitive Test Battery Scores at 24 Months Compared to Baseline | 24 months | Change in Neuro-cognitive Test Battery Scores at 24 months compared to baseline |
| Incidence of [18F]NAV4694 PET Positive Scans at 18 Months Compared to Baseline | 18 months | Incidence of \[18F\]NAV4694 PET Positive scans at 18 months compared to baseline |
| Change in Neuro-cognitive Test Battery Scores at 36 Months Compared to Baseline | 36 months | Change in Neuro-cognitive Test Battery Scores at 36 months compared to baseline |
| Change in SUVR Scores at 18 Months Compared to Baseline | 36 months | Change in SUVR scores at 18 months compared to baseline |
| Incidence of Adverse Events Post Baseline | 3 Years | Incidence of Adverse Events post baseline |
| Change in Neuro-cognitive Test Battery Scores at 30 Months Compared to Baseline | 30 months | Change in Neuro-cognitive Test Battery Scores at 30 months compared to baseline |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| [18F]NAV4694 Intravenous \[18F\]NAV4694 (8.1 mCi) administered once every 18 months
\[18F\]NAV4694 | 76 |
| Total | 76 |
Baseline characteristics
| Characteristic | [18F]NAV4694 |
|---|---|
| Age, Continuous | 76 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 66 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 72 Participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 76 |
| other Total, other adverse events | 16 / 76 |
| serious Total, serious adverse events | 14 / 76 |
Outcome results
Primary
Incidence of Mild Cognitive Impairment Progression to Alzheimer's Disease
Incidence of Mild Cognitive Impairment Progression to Alzheimer's Disease
Time frame: 3 Years
Population: Trial terminated prior to collection of sufficient information to evaluate the outcome measure. Data not collected.
Secondary
Change in Neuro-cognitive Test Battery Scores at 12 Months Compared to Baseline
Change in Neuro-cognitive Test Battery Scores at 12 months compared to baseline
Time frame: 12 months
Population: Trial terminated prior to collection of sufficient information to evaluate the outcome measure. Data not collected.
Secondary
Change in Neuro-cognitive Test Battery Scores at 18 Months Compared to Baseline
Change in Neuro-cognitive Test Battery Scores at 18 months compared to baseline
Time frame: 18 months
Population: Trial terminated prior to collection of sufficient information to evaluate the outcome measure. Data not collected.
Secondary
Change in Neuro-cognitive Test Battery Scores at 24 Months Compared to Baseline
Change in Neuro-cognitive Test Battery Scores at 24 months compared to baseline
Time frame: 24 months
Population: Trial terminated prior to collection of sufficient information to evaluate the outcome measure. Data not collected.
Secondary
Change in Neuro-cognitive Test Battery Scores at 30 Months Compared to Baseline
Change in Neuro-cognitive Test Battery Scores at 30 months compared to baseline
Time frame: 30 months
Population: Trial terminated prior to collection of sufficient information to evaluate the outcome measure. Data not collected.
Secondary
Change in Neuro-cognitive Test Battery Scores at 36 Months Compared to Baseline
Change in Neuro-cognitive Test Battery Scores at 36 months compared to baseline
Time frame: 36 months
Population: Trial terminated prior to collection of sufficient information to evaluate the outcome measure. Data not collected.
Secondary
Change in Neuro-cognitive Test Battery Scores at 6 Months Compared to Baseline
Change in Neuro-cognitive Test Battery Scores at 6 months compared to baseline
Time frame: 6 months
Population: Trial terminated prior to collection of sufficient information to evaluate the outcome measure. Data not collected.
Secondary
Change in SUVR Scores at 18 Months Compared to Baseline
Change in SUVR scores at 18 months compared to baseline
Time frame: 36 months
Population: Trial terminated prior to collection of sufficient information to evaluate the outcome measure. Data not collected.
Secondary
Incidence of [18F]NAV4694 PET Positive Scans at 18 Months Compared to Baseline
Incidence of \[18F\]NAV4694 PET Positive scans at 18 months compared to baseline
Time frame: 18 months
Population: Trial terminated prior to collection of sufficient information to evaluate the outcome measure. Data not collected.
Secondary
Incidence of Adverse Events Post Baseline
Incidence of Adverse Events post baseline
Time frame: 3 Years
Population: All participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| [18F]NAV4694 | Incidence of Adverse Events Post Baseline | 43 Post-baseline adverse events |