Alzheimer's Disease, Mild Cognitive Impairment
Conditions
Keywords
Mild Cognitive Impairment, Alzheimer's Disease, Nicotinamide, Niacinamide, Niacin, Nicotinic Acids, Vitamin, Neurodegenerative Diseases, Tauopathies, Dementia
Brief summary
The purpose of this research study is to test whether nicotinamide, also known as vitamin B3 or niacinamide, taken in high doses, can reduce phosphorylation of tau (the protein that accumulates in neurofibrillary tangles) in people with Mild Cognitive Impairment or mild Alzheimer's disease (AD) dementia.
Detailed description
Nicotinamide, the amide of nicotinic acid (vitamin B3/niacin), is an oral therapy with a wealth of clinical data in a variety of therapeutic areas, including preliminary data supporting its safety in Alzheimer's disease (AD). Preclinical work in a mouse model that develops both plaques and tangles supports the hypothesis that nicotinamide can act as a histone deacetylase (HDAC) inhibitor to reduce phosphorylation of tau. The study will implement a group sequential design, incorporating a futility analysis with a go/no-go decision conditional on cerebral spinal fluid CSF biomarker outcomes at 12-months. The primary outcome for the trial is change in p-tau231. This study timeline includes a screening phase of up to 60 days and treatment phase which is expected to last about 48 weeks and will include 4 study visits. An additional 12-month treatment and follow-up period is planned, contingent upon a go decision based on the primary outcome (CSF p-tau231) or one planned secondary outcome (CSF p-tau181)
Interventions
DRUGNicotinamide
Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.
DRUGPlacebo Comparator
Oral Tablet
Sponsors
University of California, Irvine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double-Blind-Randomized
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Mild Cognitive Impairment (MCI) or dementia due to Alzheimer's disease (AD) 2. Biomarker criteria: Cerebral Spinal Fluid (CSF) Amyloid Beta 1-42 (Aβ42) \<= 600 pg/mL, or A ratio of total tau to Aβ42 ≥ 0.39. 3. Mini-Mental State Exam (MMSE) ≥ 20 4. Blood laboratories, urinalysis, and electrocardiogram are within normal limits or deemed clinically not significant by the site investigator 5. Stable medications (including approved AD therapies) for at least 4 weeks 6. At least 6 years of education 7. Able to swallow oral tablets 8. Speaks English fluently 9. Available qualified study partner (≥3 times per week in-person communication with the participant)
Exclusion criteria
1. Active neurological or psychiatric diagnosis other than AD that may affect cognition and/or function. (Obstructive sleep apnea is permitted, if treated.) 2. Inability to undergo lumbar puncture, including use of Coumadin, novel oral anticoagulants, clopidogrel, or dipyridamole. Use of aspirin \<= 325mg daily is permitted. 3. Hachinski ischemic scale \> 4 4. Magnetic Resonance Imaging (MRI) incompatibility 5. MRI evidence of cortical stroke \>1cm, superficial siderosis, or extensive white matter hyperintensity (Cardiovascular Health Study score 7-8+) 6. Diagnosis of cancer in the previous 5 years (with the exception of basal or squamous cell carcinoma) 7. Geriatric Depression Scale (GDS) score \>6 8. History within the past 5 years of alcohol or substance use disorder 9. Laboratory evidence of a clinically significant abnormality that may interfere with study assessments 10. Active partial or total malabsorptive disease (e.g., celiac disease) 11. Resides in a skilled nursing facility 12. Participation in a clinical trial of a potential disease-modifying therapy for AD in previous 6-months (time between last investigational drug administration and baseline for the current study) 13. Pregnant, lactating or of child bearing potential (that is, women must be 2 years post-menopausal or surgically sterile to be considered not child bearing potential). 14. Unwillingness to abstain from over-the-counter nicotinamide for the duration of the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in QTC | Baseline to 48 weeks | Average within-subject change in electrocardiogram QT interval. |
| Vital Signs - BMI | Screening through end of study (week 48) | Body Mass Index (BMI) was recorded at every study visit (screening, baseline, week 12, week 24, and week 48) |
| Vital Signs - Systolic Blood Pressure | Screening through end of study (week 48) | Systolic blood pressure was recorded at every study visit (screening, baseline, week 12, week 24, and week 48) |
| Vital Signs - Diastolic Blood Pressure | Screening through end of study (week 48) | Diastolic blood pressure was recorded at every study visit (screening, baseline, week 12, week 24, and week 48) |
| Vital Signs - Pulse | Screening through end of study (week 48) | Pulse rate was recorded at every study visit (screening, baseline, week 12, week 24, and week 48) |
| Count of Treatment Emergent Adverse Events | Baseline to 48 weeks | Count of treatment emergent adverse events (TEAEs) over the duration of the study period (baseline to 48 weeks). |
| Count of Adverse Events by Severity | Baseline to 48 weeks | Count of treatment emergent adverse events (TEAEs) over the duration of the study period (baseline to 48 weeks). |
| Columbia-Suicide Severity Rating Scale | Baseline to 48 weeks | The Columbia-Suicide Severity Rating Scale (C-SSRS) captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the corresponding assessment period. The scale includes suggested questions to elicit the type of information needed to determine if a suicide-related thought or behavior occurred. The number and proportion of subjects with treatment emergent Suicidal ideation or behavior during the study period of (baseline to week 48) will be reported overall and by study arm. Treatment emergent suicidal ideation or behavior is defined as a yes answer at any time during treatment to any one of the questions in the ten suicidal ideation and behavior categories (Categories 1- 10) on the C-SSRS. Self-injurious behavior without suicidal intent, while assessed on the C-SSRS, does not form part of this outcome. |
| ECG Abnormalities | Baseline to 48 weeks | Count of participants experiencing at least one electrocardiogram (ECG) abnormality. |
| QTC Abnormalities | Baseline to 48 weeks | Count of participants experiencing at least one electrocardiogram (ECG) QT interval abnormality. Abnormal defined as above 460 for men and above 470 for women. |
| Change in P-tau 231 | Baseline to 48 weeks | Change in key peptide in cerebrospinal fluid (CSF) from baseline to 48 weeks. Higher phosphorylated tau (p-tau) is associated with a severity of Alzheimer's disease pathology. |
| Vital Signs - Weight | Screening through end of study (week 48) | Weight in kg was recorded at every study visit (screening, baseline, week 12, week 24, and week 48) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in ab40 | Baseline to 48 weeks | Change in key peptide in cerebrospinal fluid (CSF) from baseline to 48 weeks. Lower ab40 is associated with a greater probability of fibrillar amyloid burden in the brain. |
| Change in ab42 | Baseline to 48 weeks | Change in key peptide in cerebrospinal fluid (CSF) from baseline to 48 weeks. Lower ab42 is associated with a greater probability of fibrillar amyloid burden in the brain. |
| Change in P-tau 181 | Baseline to 48 weeks | Change in key peptide in cerebrospinal fluid (CSF) from baseline to 48 weeks. Higher total value is associated with greater severity of Alzheimer's disease pathology. |
| Change in Ratio of Total Tau/ab40 | Baseline to 48 weeks | Change in ratio of key peptides in cerebrospinal fluid (CSF) from baseline to 48 weeks. A lower ab40/tau ratio is associated with a higher risk of dementia. |
| Change in Ratio of Total Tau/ab42 | Baseline to 48 weeks | Change in ratio of key peptides in cerebrospinal fluid (CSF) from baseline to 48 weeks. A lower ab42/tau ratio is associated with a higher risk of dementia. |
| ADASCog-13 | Baseline to 48 weeks | ADAS-Cog13 is a structured scale that evaluates memory (immediate and delayed word recall; immediate word recognition), receptive and expressive language, orientation, ideational praxis (preparing a letter for mailing), constructional praxis (copying figures), and attention (number cancellation). Ratings of spoken language, language comprehension, word finding difficulty, and ability to remember test instructions also are obtained. Range: 0-85; higher scores indicate greater impairment. |
| Activities of Daily Living - Mild Cognitive Impairment | Baseline to 48 weeks | The ADCS-ADL-MCI is a measure of patient functional performance in Alzheimer's Disease and Mild Cognitive Impairment trials. The informant-based questionnaire assesses conduct of basic and instrumental Activities of Daily Living (ADLs). A total of 24 ADLs are evaluated. Scores range from 0 to 53, with higher scores representing more maintained function. |
| CDR Sum of Boxes | Baseline to 48 weeks | CDR-SB is a composite rating of cognition and everyday function which incorporates both informant input and direct assessment of performance. It assesses through semi-structured interview three cognitive domains (memory, orientation, and judgement/problem solving) and three everyday functional domains (community affairs, home and hobbies, personal care). Level of impairment in each of the six domains is rated from none (score=0) to severe (score=3). The six domain scores are then summed to create the CDR-SB. Range 0-18; higher scores indicate greater impairment. |
| Change in Total Tau | Baseline to 48 weeks | Change in CSF total tau in individuals with mild Alzheimer's disease (AD) dementia or Mild Cognitive Impairment due to AD. |
Countries
United States
Participant flow
Recruitment details
46 participants received at least 1 dose of study drug.
Participants by arm
| Arm | Count |
|---|---|
| Nicotinamide 1500mg twice daily: 2, 750mg tablets taken orally twice daily
Nicotinamide: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet. | 24 |
| Placebo 1500mg twice daily: 2, 750mg tablets taken orally twice daily
Placebo Comparator: Oral Tablet | 22 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Participant unwilling or unable to participate | 0 | 2 |
| Overall Study | Safety Risk | 0 | 1 |
Baseline characteristics
| Characteristic | Nicotinamide | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 74.56 years STANDARD_DEVIATION 8.97 | 72.92 years STANDARD_DEVIATION 744 | 73.78 years STANDARD_DEVIATION 8.23 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 21 Participants | 44 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Mini-Mental State Examination | 25.62 units on a scale STANDARD_DEVIATION 2.87 | 25.5 units on a scale STANDARD_DEVIATION 3.22 | 25.57 units on a scale STANDARD_DEVIATION 3.01 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 21 Participants | 21 Participants | 42 Participants |
| Region of Enrollment United States | 24 participants | 22 participants | 46 participants |
| Sex: Female, Male Female | 10 Participants | 10 Participants | 20 Participants |
| Sex: Female, Male Male | 14 Participants | 12 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 22 |
| other Total, other adverse events | 23 / 24 | 20 / 22 |
| serious Total, serious adverse events | 2 / 24 | 6 / 22 |
Outcome results
Primary
Change in P-tau 231
Change in key peptide in cerebrospinal fluid (CSF) from baseline to 48 weeks. Higher phosphorylated tau (p-tau) is associated with a severity of Alzheimer's disease pathology.
Time frame: Baseline to 48 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide | Change in P-tau 231 | 4.71 pg/ml | Standard Deviation 14.46 |
| Placebo | Change in P-tau 231 | 2.28 pg/ml | Standard Deviation 10.55 |
p-value: 0.6096ANCOVA
Primary
Change in QTC
Average within-subject change in electrocardiogram QT interval.
Time frame: Baseline to 48 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide | Change in QTC | 6.41 ms | Standard Deviation 16.02 |
| Placebo | Change in QTC | 2.1 ms | Standard Deviation 11.85 |
Primary
Columbia-Suicide Severity Rating Scale
The Columbia-Suicide Severity Rating Scale (C-SSRS) captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the corresponding assessment period. The scale includes suggested questions to elicit the type of information needed to determine if a suicide-related thought or behavior occurred. The number and proportion of subjects with treatment emergent Suicidal ideation or behavior during the study period of (baseline to week 48) will be reported overall and by study arm. Treatment emergent suicidal ideation or behavior is defined as a yes answer at any time during treatment to any one of the questions in the ten suicidal ideation and behavior categories (Categories 1- 10) on the C-SSRS. Self-injurious behavior without suicidal intent, while assessed on the C-SSRS, does not form part of this outcome.
Time frame: Baseline to 48 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nicotinamide | Columbia-Suicide Severity Rating Scale | Baseline Number of abnormal C-SSRS events | 0 events |
| Nicotinamide | Columbia-Suicide Severity Rating Scale | Post-baseline number of abnormal C-SSRS events | 1 events |
| Placebo | Columbia-Suicide Severity Rating Scale | Baseline Number of abnormal C-SSRS events | 3 events |
| Placebo | Columbia-Suicide Severity Rating Scale | Post-baseline number of abnormal C-SSRS events | 3 events |
Primary
Count of Adverse Events by Severity
Count of treatment emergent adverse events (TEAEs) over the duration of the study period (baseline to 48 weeks).
Time frame: Baseline to 48 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nicotinamide | Count of Adverse Events by Severity | Mild | 49 events |
| Nicotinamide | Count of Adverse Events by Severity | Moderate | 27 events |
| Nicotinamide | Count of Adverse Events by Severity | Severe | 3 events |
| Nicotinamide | Count of Adverse Events by Severity | Total | 79 events |
| Placebo | Count of Adverse Events by Severity | Total | 71 events |
| Placebo | Count of Adverse Events by Severity | Mild | 38 events |
| Placebo | Count of Adverse Events by Severity | Severe | 2 events |
| Placebo | Count of Adverse Events by Severity | Moderate | 31 events |
Primary
Count of Treatment Emergent Adverse Events
Count of treatment emergent adverse events (TEAEs) over the duration of the study period (baseline to 48 weeks).
Time frame: Baseline to 48 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nicotinamide | Count of Treatment Emergent Adverse Events | 79 events |
| Placebo | Count of Treatment Emergent Adverse Events | 71 events |
Primary
ECG Abnormalities
Count of participants experiencing at least one electrocardiogram (ECG) abnormality.
Time frame: Baseline to 48 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nicotinamide | ECG Abnormalities | 24 Participants |
| Placebo | ECG Abnormalities | 20 Participants |
Primary
QTC Abnormalities
Count of participants experiencing at least one electrocardiogram (ECG) QT interval abnormality. Abnormal defined as above 460 for men and above 470 for women.
Time frame: Baseline to 48 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nicotinamide | QTC Abnormalities | 2 Participants |
| Placebo | QTC Abnormalities | 1 Participants |
Primary
Vital Signs - BMI
Body Mass Index (BMI) was recorded at every study visit (screening, baseline, week 12, week 24, and week 48)
Time frame: Screening through end of study (week 48)
Population: Numbers analyzed in some rows lower due to missing data (visit not completed, or participant refused measure).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nicotinamide | Vital Signs - BMI | Baseline Visit | 26.33 kg/m^2 | Standard Deviation 4.69 |
| Nicotinamide | Vital Signs - BMI | Week 24 Visit | 26.52 kg/m^2 | Standard Deviation 4.56 |
| Nicotinamide | Vital Signs - BMI | Week 12 Visit | 26.42 kg/m^2 | Standard Deviation 4.51 |
| Nicotinamide | Vital Signs - BMI | Week 48 Visit | 26.24 kg/m^2 | Standard Deviation 4.75 |
| Nicotinamide | Vital Signs - BMI | Screening Visit | 26.35 kg/m^2 | Standard Deviation 4.75 |
| Placebo | Vital Signs - BMI | Week 48 Visit | 24.68 kg/m^2 | Standard Deviation 3.68 |
| Placebo | Vital Signs - BMI | Screening Visit | 24.09 kg/m^2 | Standard Deviation 4.17 |
| Placebo | Vital Signs - BMI | Baseline Visit | 24.85 kg/m^2 | Standard Deviation 3.43 |
| Placebo | Vital Signs - BMI | Week 12 Visit | 24.72 kg/m^2 | Standard Deviation 3.79 |
| Placebo | Vital Signs - BMI | Week 24 Visit | 25.08 kg/m^2 | Standard Deviation 3.68 |
Primary
Vital Signs - Diastolic Blood Pressure
Diastolic blood pressure was recorded at every study visit (screening, baseline, week 12, week 24, and week 48)
Time frame: Screening through end of study (week 48)
Population: Numbers analyzed in some rows lower due to missing data (visit not completed, or participant refused measure).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nicotinamide | Vital Signs - Diastolic Blood Pressure | Baseline Visit | 74.21 mm Hg | Standard Deviation 11.87 |
| Nicotinamide | Vital Signs - Diastolic Blood Pressure | Week 24 Visit | 75.2 mm Hg | Standard Deviation 7.35 |
| Nicotinamide | Vital Signs - Diastolic Blood Pressure | Week 12 Visit | 72.45 mm Hg | Standard Deviation 7.61 |
| Nicotinamide | Vital Signs - Diastolic Blood Pressure | Week 48 Visit | 71.9 mm Hg | Standard Deviation 10.4 |
| Nicotinamide | Vital Signs - Diastolic Blood Pressure | Screening Visit | 75.42 mm Hg | Standard Deviation 9.31 |
| Placebo | Vital Signs - Diastolic Blood Pressure | Week 48 Visit | 69.74 mm Hg | Standard Deviation 8.53 |
| Placebo | Vital Signs - Diastolic Blood Pressure | Screening Visit | 71.32 mm Hg | Standard Deviation 8.97 |
| Placebo | Vital Signs - Diastolic Blood Pressure | Baseline Visit | 70.45 mm Hg | Standard Deviation 8.78 |
| Placebo | Vital Signs - Diastolic Blood Pressure | Week 12 Visit | 71.4 mm Hg | Standard Deviation 10.23 |
| Placebo | Vital Signs - Diastolic Blood Pressure | Week 24 Visit | 71.4 mm Hg | Standard Deviation 10.23 |
Primary
Vital Signs - Pulse
Pulse rate was recorded at every study visit (screening, baseline, week 12, week 24, and week 48)
Time frame: Screening through end of study (week 48)
Population: Numbers analyzed in some rows lower due to missing data (visit not completed, or participant refused measure).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nicotinamide | Vital Signs - Pulse | Baseline Visit | 59.33 bpm | Standard Deviation 12.85 |
| Nicotinamide | Vital Signs - Pulse | Week 24 Visit | 58.6 bpm | Standard Deviation 7.42 |
| Nicotinamide | Vital Signs - Pulse | Week 12 Visit | 58.86 bpm | Standard Deviation 6.14 |
| Nicotinamide | Vital Signs - Pulse | Week 48 Visit | 59.57 bpm | Standard Deviation 8.33 |
| Nicotinamide | Vital Signs - Pulse | Screening Visit | 56.42 bpm | Standard Deviation 6.98 |
| Placebo | Vital Signs - Pulse | Week 48 Visit | 64.84 bpm | Standard Deviation 12.65 |
| Placebo | Vital Signs - Pulse | Screening Visit | 62.5 bpm | Standard Deviation 10.92 |
| Placebo | Vital Signs - Pulse | Baseline Visit | 64.91 bpm | Standard Deviation 8.78 |
| Placebo | Vital Signs - Pulse | Week 12 Visit | 63.45 bpm | Standard Deviation 11.65 |
| Placebo | Vital Signs - Pulse | Week 24 Visit | 62.26 bpm | Standard Deviation 8.75 |
Primary
Vital Signs - Systolic Blood Pressure
Systolic blood pressure was recorded at every study visit (screening, baseline, week 12, week 24, and week 48)
Time frame: Screening through end of study (week 48)
Population: Numbers analyzed in some rows lower due to missing data (visit not completed, or participant refused measure).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nicotinamide | Vital Signs - Systolic Blood Pressure | Baseline Visit | 137.42 mm Hg | Standard Deviation 15.99 |
| Nicotinamide | Vital Signs - Systolic Blood Pressure | Week 24 Visit | 130.4 mm Hg | Standard Deviation 14.04 |
| Nicotinamide | Vital Signs - Systolic Blood Pressure | Week 12 Visit | 133.36 mm Hg | Standard Deviation 14.91 |
| Nicotinamide | Vital Signs - Systolic Blood Pressure | Week 48 Visit | 129.43 mm Hg | Standard Deviation 17.76 |
| Nicotinamide | Vital Signs - Systolic Blood Pressure | Screening Visit | 134.67 mm Hg | Standard Deviation 19.17 |
| Placebo | Vital Signs - Systolic Blood Pressure | Week 48 Visit | 129.37 mm Hg | Standard Deviation 17.16 |
| Placebo | Vital Signs - Systolic Blood Pressure | Screening Visit | 126.09 mm Hg | Standard Deviation 14.32 |
| Placebo | Vital Signs - Systolic Blood Pressure | Baseline Visit | 125.41 mm Hg | Standard Deviation 17.66 |
| Placebo | Vital Signs - Systolic Blood Pressure | Week 12 Visit | 128.05 mm Hg | Standard Deviation 18.61 |
| Placebo | Vital Signs - Systolic Blood Pressure | Week 24 Visit | 130.16 mm Hg | Standard Deviation 13.12 |
Primary
Vital Signs - Weight
Weight in kg was recorded at every study visit (screening, baseline, week 12, week 24, and week 48)
Time frame: Screening through end of study (week 48)
Population: Numbers analyzed in some rows lower due to missing data (visit not completed, or participant refused measure).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nicotinamide | Vital Signs - Weight | Baseline Visit | 76.29 kg | Standard Deviation 12.57 |
| Nicotinamide | Vital Signs - Weight | Week 24 Visit | 76.88 kg | Standard Deviation 11.49 |
| Nicotinamide | Vital Signs - Weight | Week 12 Visit | 77.27 kg | Standard Deviation 10.86 |
| Nicotinamide | Vital Signs - Weight | Week 48 Visit | 76.43 kg | Standard Deviation 11.96 |
| Nicotinamide | Vital Signs - Weight | Screening Visit | 76.39 kg | Standard Deviation 12.99 |
| Placebo | Vital Signs - Weight | Week 48 Visit | 70.27 kg | Standard Deviation 12.2 |
| Placebo | Vital Signs - Weight | Screening Visit | 68.11 kg | Standard Deviation 14.3 |
| Placebo | Vital Signs - Weight | Baseline Visit | 70.05 kg | Standard Deviation 11.86 |
| Placebo | Vital Signs - Weight | Week 12 Visit | 69.36 kg | Standard Deviation 12.67 |
| Placebo | Vital Signs - Weight | Week 24 Visit | 72.22 kg | Standard Deviation 11.35 |
Secondary
Activities of Daily Living - Mild Cognitive Impairment
The ADCS-ADL-MCI is a measure of patient functional performance in Alzheimer's Disease and Mild Cognitive Impairment trials. The informant-based questionnaire assesses conduct of basic and instrumental Activities of Daily Living (ADLs). A total of 24 ADLs are evaluated. Scores range from 0 to 53, with higher scores representing more maintained function.
Time frame: Baseline to 48 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide | Activities of Daily Living - Mild Cognitive Impairment | -4.05 score on a scale | Standard Deviation 4.88 |
| Placebo | Activities of Daily Living - Mild Cognitive Impairment | -1.39 score on a scale | Standard Deviation 6.06 |
p-value: 0.1008Mixed Models Analysis
Secondary
ADASCog-13
ADAS-Cog13 is a structured scale that evaluates memory (immediate and delayed word recall; immediate word recognition), receptive and expressive language, orientation, ideational praxis (preparing a letter for mailing), constructional praxis (copying figures), and attention (number cancellation). Ratings of spoken language, language comprehension, word finding difficulty, and ability to remember test instructions also are obtained. Range: 0-85; higher scores indicate greater impairment.
Time frame: Baseline to 48 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide | ADASCog-13 | 3.2 score on a scale | Standard Deviation 5.72 |
| Placebo | ADASCog-13 | 5.16 score on a scale | Standard Deviation 7.46 |
p-value: 0.3233Mixed Models Analysis
Secondary
CDR Sum of Boxes
CDR-SB is a composite rating of cognition and everyday function which incorporates both informant input and direct assessment of performance. It assesses through semi-structured interview three cognitive domains (memory, orientation, and judgement/problem solving) and three everyday functional domains (community affairs, home and hobbies, personal care). Level of impairment in each of the six domains is rated from none (score=0) to severe (score=3). The six domain scores are then summed to create the CDR-SB. Range 0-18; higher scores indicate greater impairment.
Time frame: Baseline to 48 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide | CDR Sum of Boxes | 0.76 score on a scale | Standard Deviation 2.03 |
| Placebo | CDR Sum of Boxes | 2.18 score on a scale | Standard Deviation 2.82 |
p-value: 0.0323Mixed Models Analysis
Secondary
Change in ab40
Change in key peptide in cerebrospinal fluid (CSF) from baseline to 48 weeks. Lower ab40 is associated with a greater probability of fibrillar amyloid burden in the brain.
Time frame: Baseline to 48 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide | Change in ab40 | 2307 pg/ml | Standard Deviation 2516.4 |
| Placebo | Change in ab40 | 1961.1 pg/ml | Standard Deviation 4252.97 |
p-value: 0.648ANCOVA
Secondary
Change in ab42
Change in key peptide in cerebrospinal fluid (CSF) from baseline to 48 weeks. Lower ab42 is associated with a greater probability of fibrillar amyloid burden in the brain.
Time frame: Baseline to 48 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide | Change in ab42 | 127.74 pg/ml | Standard Deviation 161.54 |
| Placebo | Change in ab42 | 113.79 pg/ml | Standard Deviation 321.92 |
p-value: 0.6833ANCOVA
Secondary
Change in P-tau 181
Change in key peptide in cerebrospinal fluid (CSF) from baseline to 48 weeks. Higher total value is associated with greater severity of Alzheimer's disease pathology.
Time frame: Baseline to 48 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide | Change in P-tau 181 | -0.41 pg/ml | Standard Deviation 29.83 |
| Placebo | Change in P-tau 181 | -10.43 pg/ml | Standard Deviation 41.79 |
p-value: 0.4438ANCOVA
Secondary
Change in Ratio of Total Tau/ab40
Change in ratio of key peptides in cerebrospinal fluid (CSF) from baseline to 48 weeks. A lower ab40/tau ratio is associated with a higher risk of dementia.
Time frame: Baseline to 48 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide | Change in Ratio of Total Tau/ab40 | -0.02 ratio | Standard Deviation 0.02 |
| Placebo | Change in Ratio of Total Tau/ab40 | -0.02 ratio | Standard Deviation 0.02 |
p-value: 0.93428359ANCOVA
Secondary
Change in Ratio of Total Tau/ab42
Change in ratio of key peptides in cerebrospinal fluid (CSF) from baseline to 48 weeks. A lower ab42/tau ratio is associated with a higher risk of dementia.
Time frame: Baseline to 48 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide | Change in Ratio of Total Tau/ab42 | -0.46 ratio | Standard Deviation 0.56 |
| Placebo | Change in Ratio of Total Tau/ab42 | -0.5 ratio | Standard Deviation 0.55 |
p-value: 0.9931ANCOVA
Secondary
Change in Total Tau
Change in CSF total tau in individuals with mild Alzheimer's disease (AD) dementia or Mild Cognitive Impairment due to AD.
Time frame: Baseline to 48 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotinamide | Change in Total Tau | -8.42 pg/ml | Standard Deviation 228.59 |
| Placebo | Change in Total Tau | -60.47 pg/ml | Standard Deviation 237.54 |
p-value: 0.7158ANCOVA