Trial Outcomes & Findings for A Pilot Clinical Trial of Exendin-4 in Alzheimer's Disease (NCT NCT01255163)
NCT ID: NCT01255163
Last Updated: 2018-02-22
Results Overview
Tolerability of exenatide (nausea is the most common expected adverse event of exenatide)
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
57 participants
Primary outcome timeframe
18 months
Results posted on
2018-02-22
Participant Flow
Recruitment took place between 10/5/2010 and 7/25/2016. A total of 57 participants signed informed consent to undergo screening procedures. Of those, 28 qualified, 1 withdrew prior to randomization, 27 were randomized to exenatide or placebo, and 18 completed the study.
The study includes a baseline visit to determine eligibility. Therefore, 57 participants were enrolled (i.e. signed informed consent prior to screening). Of those, 28 qualified, 1 withdrew prior to randomization, 27 were randomized to exenatide or placebo, and 18 completed the study.
Participant milestones
| Measure |
Exendin-4
Exenatide 5 mcg or 10 mcg SC twice daily
|
Placebo
Placebo SC twice daily
|
|---|---|---|
|
Overall Study
STARTED
|
13
|
14
|
|
Overall Study
COMPLETED
|
9
|
9
|
|
Overall Study
NOT COMPLETED
|
4
|
5
|
Reasons for withdrawal
| Measure |
Exendin-4
Exenatide 5 mcg or 10 mcg SC twice daily
|
Placebo
Placebo SC twice daily
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
2
|
0
|
|
Overall Study
Adverse Event
|
0
|
2
|
|
Overall Study
AstraZeneca stopped support of the study
|
1
|
3
|
Baseline Characteristics
A Pilot Clinical Trial of Exendin-4 in Alzheimer's Disease
Baseline characteristics by cohort
| Measure |
Exendin-4
n=13 Participants
Exenatide 5 mcg or 10 mcg SC twice daily
|
Placebo
n=14 Participants
Placebo SC twice daily
|
Total
n=27 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
70.46 years
STANDARD_DEVIATION 7.137 • n=99 Participants
|
74.64 years
STANDARD_DEVIATION 7.034 • n=107 Participants
|
72.63 years
STANDARD_DEVIATION 7.265 • n=206 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=99 Participants
|
9 Participants
n=107 Participants
|
15 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
13 Participants
n=99 Participants
|
14 Participants
n=107 Participants
|
27 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
12 Participants
n=99 Participants
|
12 Participants
n=107 Participants
|
24 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
13 participants
n=99 Participants
|
14 participants
n=107 Participants
|
27 participants
n=206 Participants
|
|
Cerebrospinal fluid amyloid-beta 42 (CSF Abeta42)
|
158.85 pg/dl
STANDARD_DEVIATION 43.619 • n=99 Participants
|
158.86 pg/dl
STANDARD_DEVIATION 33.558 • n=107 Participants
|
158.85 pg/dl
STANDARD_DEVIATION 37.963 • n=206 Participants
|
|
Mini Mental State Examination (MMSE)
|
25.85 units on a scale
STANDARD_DEVIATION 3.997 • n=99 Participants
|
24.64 units on a scale
STANDARD_DEVIATION 5.198 • n=107 Participants
|
25.22 units on a scale
STANDARD_DEVIATION 4.61 • n=206 Participants
|
|
Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog70)
|
14.46 units on a scale
STANDARD_DEVIATION 6.654 • n=99 Participants
|
13.64 units on a scale
STANDARD_DEVIATION 6.879 • n=107 Participants
|
14.04 units on a scale
STANDARD_DEVIATION 6.653 • n=206 Participants
|
|
Body Mass Index (BMI)
|
26.631 kg/m^2
STANDARD_DEVIATION 3.3673 • n=99 Participants
|
26.85 kg/m^2
STANDARD_DEVIATION 5.2611 • n=107 Participants
|
26.744 kg/m^2
STANDARD_DEVIATION 4.3687 • n=206 Participants
|
|
Fasting glucose
|
94.92 mg/dl
STANDARD_DEVIATION 8.311 • n=99 Participants
|
90.14 mg/dl
STANDARD_DEVIATION 9.206 • n=107 Participants
|
92.44 mg/dl
STANDARD_DEVIATION 8.954 • n=206 Participants
|
|
Fasting insulin
|
8.53 uIU/ml
STANDARD_DEVIATION 4.4337 • n=99 Participants
|
8.1 uIU/ml
STANDARD_DEVIATION 4.5361 • n=107 Participants
|
8.254 uIU/ml
STANDARD_DEVIATION 4.4628 • n=206 Participants
|
|
Cerebrospinal fluid phospho181-tau (CSF p181-tau)
|
56.62 pg/dl
STANDARD_DEVIATION 34.606 • n=99 Participants
|
40.64 pg/dl
STANDARD_DEVIATION 16.137 • n=107 Participants
|
48.33 pg/dl
STANDARD_DEVIATION 27.369 • n=206 Participants
|
|
Cerebrospinal fluid (CSF) Total Tau
|
90.38 pg/dl
STANDARD_DEVIATION 53.053 • n=99 Participants
|
70.64 pg/dl
STANDARD_DEVIATION 22.802 • n=107 Participants
|
80.15 pg/dl
STANDARD_DEVIATION 40.744 • n=206 Participants
|
|
Clinical Dementia Rating (CDR) global score
|
0.577 units on a scale
STANDARD_DEVIATION 0.2774 • n=99 Participants
|
0.607 units on a scale
STANDARD_DEVIATION 0.2129 • n=107 Participants
|
0.593 units on a scale
STANDARD_DEVIATION 0.2417 • n=206 Participants
|
|
Clinical Dementia Rating (CDR) sum of boxes
|
2.769 units on a scale
STANDARD_DEVIATION 1.775 • n=99 Participants
|
3 units on a scale
STANDARD_DEVIATION 1.7759 • n=107 Participants
|
2.889 units on a scale
STANDARD_DEVIATION 1.745 • n=206 Participants
|
|
Nausea
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 18 monthsTolerability of exenatide (nausea is the most common expected adverse event of exenatide)
Outcome measures
| Measure |
Exendin-4
n=13 Participants
Exenatide 5 mcg or 10 mcg SC twice daily
|
Placebo
n=14 Participants
Placebo SC twice daily
|
|---|---|---|
|
Number of Participants With Incidence of Nausea
|
5 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 18 monthsScale range: 0 - 30 points (higher is better)
Outcome measures
| Measure |
Exendin-4
n=13 Participants
Exenatide 5 mcg or 10 mcg SC twice daily
|
Placebo
n=14 Participants
Placebo SC twice daily
|
|---|---|---|
|
Mini Mental State Examination (MMSE)
|
23.11 units on a scale
Standard Deviation 6.009
|
23.11 units on a scale
Standard Deviation 5.011
|
SECONDARY outcome
Timeframe: 18 monthsAlzheimer's dementia scale cognitive sub-scale range: 0 - 70 points (higher is worse)
Outcome measures
| Measure |
Exendin-4
n=9 Participants
Exenatide 5 mcg or 10 mcg SC twice daily
|
Placebo
n=9 Participants
Placebo SC twice daily
|
|---|---|---|
|
Alzheimer's Disease Assessment Scale-cognitive Subscale (ADAS-cog70)
|
16 units on a scale
Standard Deviation 8.588
|
17.78 units on a scale
Standard Deviation 8.643
|
SECONDARY outcome
Timeframe: 18 monthsClinical Dementia Rating global score range: 0 (no dementia); 0.5 (Mild Cognitive Impairment); 1 (mild dementia); 2 (moderate dementia); 3 (severe dementia). Higher is worse.
Outcome measures
| Measure |
Exendin-4
n=9 Participants
Exenatide 5 mcg or 10 mcg SC twice daily
|
Placebo
n=9 Participants
Placebo SC twice daily
|
|---|---|---|
|
Clinical Dementia Rating (CDR) Global Score
|
0.889 units on a scale
Standard Deviation 0.6509
|
0.833 units on a scale
Standard Deviation 0.5
|
SECONDARY outcome
Timeframe: 18 monthsSum of the Clinical Dementia Rating "boxes" (memory, orientation, judgment and problem solving, community affairs, home and hobbies, personal care). Each box is rated as 0, 0.5, 1, 2 or 3. Range for the sum of boxes is 0 - 18. Higher scores reflect a greater severity of dementia.
Outcome measures
| Measure |
Exendin-4
n=9 Participants
Exenatide 5 mcg or 10 mcg SC twice daily
|
Placebo
n=9 Participants
Placebo SC twice daily
|
|---|---|---|
|
Clinical Dementia Rating (CDR) Sum of Boxes
|
4.778 units on a scale
Standard Deviation 4.0782
|
4.5 units on a scale
Standard Deviation 2.3318
|
SECONDARY outcome
Timeframe: 18 monthsTotal Tau measured in CSF using Luminex xMAP technology and INNO-BIA Alz Bio3 kits (Research Use Only) provided by Fujirebio
Outcome measures
| Measure |
Exendin-4
n=9 Participants
Exenatide 5 mcg or 10 mcg SC twice daily
|
Placebo
n=9 Participants
Placebo SC twice daily
|
|---|---|---|
|
Cerebrospinal Fluid (CSF) Total Tau
|
86.57 pg/dl
Standard Deviation 37.434
|
70.75 pg/dl
Standard Deviation 33.148
|
SECONDARY outcome
Timeframe: 18 monthsp-181-Tau measured in CSF using Luminex xMAP technology and INNO-BIA Alz Bio3 kits (Research Use Only) provided by Fujirebio
Outcome measures
| Measure |
Exendin-4
n=9 Participants
Exenatide 5 mcg or 10 mcg SC twice daily
|
Placebo
n=9 Participants
Placebo SC twice daily
|
|---|---|---|
|
Cerebrospinal Fluid phospho181-tau (CSF p181-tau)
|
54.57 pg/dl
Standard Deviation 32.893
|
44.25 pg/dl
Standard Deviation 19.739
|
SECONDARY outcome
Timeframe: 18 monthsAbeta42 peptide measured in CSF using Luminex xMAP technology and INNO-BIA Alz Bio3 kits (Research Use Only) provided by Fujirebio
Outcome measures
| Measure |
Exendin-4
n=9 Participants
Exenatide 5 mcg or 10 mcg SC twice daily
|
Placebo
n=9 Participants
Placebo SC twice daily
|
|---|---|---|
|
Cerebrospinal Fluid Amyloid-beta 42 (CSF Abeta42)
|
177.43 pg/dl
Standard Deviation 70.720
|
176.38 pg/dl
Standard Deviation 30.528
|
SECONDARY outcome
Timeframe: 18 monthsBody Mass Index defined as a person's weight in kilograms (kg) divided by his or her height in meters squared.
Outcome measures
| Measure |
Exendin-4
n=9 Participants
Exenatide 5 mcg or 10 mcg SC twice daily
|
Placebo
n=9 Participants
Placebo SC twice daily
|
|---|---|---|
|
Body Mass Index (BMI)
|
25.867 kg/m^2
Standard Deviation 3.6284
|
25.789 kg/m^2
Standard Deviation 4.6023
|
Adverse Events
Exendin-4
Serious events: 1 serious events
Other events: 13 other events
Deaths: 0 deaths
Placebo
Serious events: 1 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Exendin-4
n=13 participants at risk
Exenatide 5 mcg or 10 mcg SC twice daily
|
Placebo
n=14 participants at risk
Placebo SC twice daily
|
|---|---|---|
|
Cardiac disorders
Myocardiac Infarction
|
7.7%
1/13 • Number of events 1 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
0.00%
0/14 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
|
Respiratory, thoracic and mediastinal disorders
Lung cancer
|
0.00%
0/13 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
7.1%
1/14 • Number of events 1 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
Other adverse events
| Measure |
Exendin-4
n=13 participants at risk
Exenatide 5 mcg or 10 mcg SC twice daily
|
Placebo
n=14 participants at risk
Placebo SC twice daily
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
38.5%
5/13 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
0.00%
0/14 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
15.4%
2/13 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
7.1%
1/14 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
|
Gastrointestinal disorders
Lower abdominal pain
|
7.7%
1/13 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
0.00%
0/14 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
|
Gastrointestinal disorders
Pancreatic enzyme elevation
|
15.4%
2/13 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
14.3%
2/14 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
|
Gastrointestinal disorders
Diarrhea
|
23.1%
3/13 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
7.1%
1/14 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
|
Metabolism and nutrition disorders
Loss of appetite/weight loss
|
30.8%
4/13 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
0.00%
0/14 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
|
Metabolism and nutrition disorders
Hypoglycemia symptoms
|
23.1%
3/13 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
14.3%
2/14 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
|
Skin and subcutaneous tissue disorders
Injection site ecchymosis and pain
|
7.7%
1/13 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
7.1%
1/14 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
|
Renal and urinary disorders
Abnormal kidney function tests
|
15.4%
2/13 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
14.3%
2/14 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
|
General disorders
Fatigue
|
15.4%
2/13 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
0.00%
0/14 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
|
Endocrine disorders
Thyroid abnormalities
|
7.7%
1/13 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
14.3%
2/14 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
|
Injury, poisoning and procedural complications
Post lumbar puncture headache
|
23.1%
3/13 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
21.4%
3/14 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
|
Musculoskeletal and connective tissue disorders
Orthopedic injuries
|
15.4%
2/13 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
14.3%
2/14 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
|
Injury, poisoning and procedural complications
Vomiting
|
7.7%
1/13 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
0.00%
0/14 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
|
Nervous system disorders
Vasovagal syncope
|
15.4%
2/13 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
0.00%
0/14 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
|
Nervous system disorders
Lacunar stroke
|
0.00%
0/13 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
7.1%
1/14 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
|
Musculoskeletal and connective tissue disorders
Gout
|
7.7%
1/13 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
0.00%
0/14 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
|
Infections and infestations
Influenza
|
7.7%
1/13 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
0.00%
0/14 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
|
Ear and labyrinth disorders
Tinnitus
|
7.7%
1/13 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
0.00%
0/14 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
|
Eye disorders
Allergic conjuctivitis
|
7.7%
1/13 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
0.00%
0/14 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
|
Eye disorders
Floaters
|
0.00%
0/13 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
7.1%
1/14 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
|
Cardiac disorders
Dyspnea on exertion
|
0.00%
0/13 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
7.1%
1/14 • Up to 18 months
Description of AEs according to clinicaltrials.gov definitions
|
Additional Information
Dimitrios Kapogiannis, Clinical Investigator
National Institute on Aging (NIA/NIH)
Phone: 410-350-3953
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place