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Effects of Atomoxetine in Mild Cognitive Impairment (ATX-001)

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ClinicalTrials.gov Identifier: NCT01522404
Recruitment Status : Completed
First Posted : January 31, 2012
Results First Posted : December 5, 2018
Last Update Posted : December 5, 2018
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Allan I Levey, MD, Emory University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Basic Science
Condition Mild Cognitive Impairment
Interventions Drug: Atomoxetine
Drug: Placebo
Enrollment 39
Recruitment Details Participants were recruited between March 2012 and October 2017. The study is conducted at Emory University Hospital in Atlanta.
Pre-assignment Details  
Arm/Group Title Atomoxetine / Inactive Compound Inactive Compound / Atomoxetine
Hide Arm/Group Description Participants in this group are randomized to Atomoxetine, starting with 10 mg po daily and increasing weekly by increments to a maximum of 100 mg po daily or the maximum tolerated dose during period 1/ Matching placebo that have inactive compound during period 2. Participants in this group are randomized to matching placebo that have inactive compound during period 1/ Atomoxetine, starting with 10 mg po daily and increasing weekly by increments to a maximum of 100 mg po daily or the maximum tolerated dose during period 2.
Period Title: First Intervention (up to Week 29)
Started 20 19
Completed 18 19
Not Completed 2 0
Reason Not Completed
Withdrawal by Subject             1             0
Adverse Event             1             0
Period Title: Second Intervention (up to Week 58)
Started 18 19
Completed 17 19
Not Completed 1 0
Reason Not Completed
Withdrawal by Subject             1             0
Arm/Group Title Atomoxetine / Inactive Compound Inactive Compound / Atomoxetine Total
Hide Arm/Group Description Participants in this group are randomized to Atomoxetine, starting with 10 mg po daily and increasing weekly by increments to a maximum of 100 mg po daily or the maximum tolerated dose during period 1/ Matching placebo that have inactive compound during period 2. Participants in this group are randomized to matching placebo that have inactive compound during period 1/ Atomoxetine, starting with 10 mg po daily and increasing weekly by increments to a maximum of 100 mg po daily or the maximum tolerated dose during period 2. Total of all reporting groups
Overall Number of Baseline Participants 20 19 39
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 19 participants 39 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
4
  20.0%
3
  15.8%
7
  17.9%
>=65 years
16
  80.0%
16
  84.2%
32
  82.1%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 20 participants 19 participants 39 participants
70.2  (5.7) 72.0  (7.5) 71.1  (6.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 19 participants 39 participants
Female
10
  50.0%
8
  42.1%
18
  46.2%
Male
10
  50.0%
11
  57.9%
21
  53.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 19 participants 39 participants
Hispanic or Latino
1
   5.0%
0
   0.0%
1
   2.6%
Not Hispanic or Latino
19
  95.0%
19
 100.0%
38
  97.4%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 19 participants 39 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
20
 100.0%
19
 100.0%
39
 100.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 20 participants 19 participants 39 participants
20 19 39
1.Primary Outcome
Title Change in Interleukin 1 (IL 1-alpha) in Cerebrospinal Fluid (CSF) in Subjects With Mild Cognitive Impairment (MCI) Treated With Atomoxetine/Inactive Compound Compared to Subjects Treated With Inactive Compound / Atomoxetine
Hide Description This study will examine the effects of Atomoxetine and Inactive compound on biomarkers of inflammation by measuring and comparing the levels of Interleukin 1 (IL 1-alpha) using the assay of CSF at Baseline, Week 29 and Week 58 among the two groups. The study hypothesizes that the period that participants are treated with atomoxetine will have reductions in levels of these pro-inflammatory biomarkers among the two groups.
Time Frame Baseline, Week 29 and Week 58
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Only 15.1 % of the samples were above the limit of detection for Interleukin 1 (IL 1-alpha) alpha in CSF, precluding the planned analysis and comparing the mean and standard deviation of Interleukin 1 (IL 1-alpha) alpha levels in treatment versus placebo groups. Hence the analysis was not done and the outcome was not measured.
Arm/Group Title Atomoxetine / Inactive Compound Inactive Compound / Atomoxetine
Hide Arm/Group Description:
Participants in this group are randomized to Atomoxetine, starting with 10 mg po daily and increasing weekly by increments to a maximum of 100 mg po daily or the maximum tolerated dose during period 1/ Matching placebo that have inactive compound during period 2.
Participants in this group are randomized to matching placebo that have inactive compound during period 1/ Atomoxetine, starting with 10 mg po daily and increasing weekly by increments to a maximum of 100 mg po daily or the maximum tolerated dose during period 2.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
2.Primary Outcome
Title Change in Mean Level of Thymus-Expressed Chemokine (TECK) in Cerebrospinal Fluid (CSF) in Participants With Mild Cognitive Impairment (MCI) Treated With Atomoxetine / Inactive Compound Compared to Participants Treated With Inactive Compound / Atomoxetine
Hide Description This study will examine the effect of Atomoxetine and Inactive Compound on biomarkers of inflammation by measuring and comparing the mean levels of Thymus-Expressed Chemokine (TECK). These levels are measured using the assay of CSF at Baseline, Week 29 and Week 58. The study hypothesizes that the period that participants are treated with atomoxetine will have reduction in levels of these markers among both groups.
Time Frame Baseline, Week 29 and Week 58
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Only 49.1 % of the samples were above the limit of detection for TECK in CSF among the groups that are included in the analysis below. The levels for only 18 participants in Atomoxetine group and 18 participants in Inactive compound were analyzed
Arm/Group Title Atomoxetine Inactive Compound / Placebo
Hide Arm/Group Description:
Participants in this group received Atomoxetine, starting with 10 mg po daily and increasing weekly by increments to a maximum of 100 mg po daily or the maximum tolerated dose.
Participants in this group receive matching placebo that have inactive compound
Overall Number of Participants Analyzed 18 18
Mean (Standard Deviation)
Unit of Measure: pg/mL
Baseline 1  (0.4) 0.8  (0.2)
Week 29 1  (0.4) 0.9  (0.2)
Week 58 1.1  (0.7) 0.9  (0.3)
3.Primary Outcome
Title Number of All Adverse Events Among the Participants With Mild Cognitive Impairment (MCI) Treated With Atomoxetine Compared to the Participants Treated With Placebo/Inactive Compound
Hide Description Safety was assessed by number of all adverse events among the participants treated with Atomoxetine compared to the participants treated with Placebo throughout the study. The Adverse Event assessment was done at each study visit through their participation in the study.
Time Frame Up to Week 58
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

In Atomoxetine/Placebo group 20 participants got Atomoxetine during period 1 and 18 got Placebo during period 2.

In Placebo/ Atomoxetine group 19 participants got Placebo during period 1 and 19 participants got Atomoxetine during period 2.

Total for Atomoxetine (20 in period 1 + 19 in period 2) Total for Placebo (19 in period 1+ 18 in period 2)

Arm/Group Title Atomoxetine Inactive Compound (Placebo)
Hide Arm/Group Description:
Participants in this arm received Atomoxetine, starting with 10 mg po daily and increasing weekly by increments to a maximum of 100 mg po daily or the maximum tolerated dose
Participants in this arm will receive a matching placebo that have inactive compound.
Overall Number of Participants Analyzed 39 37
Measure Type: Number
Unit of Measure: Adverse events
142 91
4.Primary Outcome
Title Number of Participants That Drop Out of the Study Among the Participants Treated With Atomoxetine When Compared to the Participants Treated With Inactive Compound (Placebo)
Hide Description Tolerability is measured by comparing the drop out rate among the participants treated with Atomoxetine to the participants treated with inactive compound (Placebo). Study predicts that treatment-associated (Atomoxetine Group) drop out rate will be < 15% .
Time Frame Up to Week 58
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

In Atomoxetine/Placebo group 20 participants got Atomoxetine during period 1 and 18 got Placebo during period 2.

In Placebo/ Atomoxetine group 19 participants got Placebo during period 1 and 19 participants got Atomoxetine during period 2.

Total for Atomoxetine (20 in period 1 + 19 in period 2) Total for Placebo (19 in period 1+ 18 in period 2)

Arm/Group Title Atomoxetine Inactive Compound/Placebo
Hide Arm/Group Description:
Participants in this group received Atomoxetine starting with 10 mg po daily and increasing weekly by increments to a maximum of 100 mg po daily or the maximum tolerated dose.
Participants in this group received Matching placebo that have inactive compound.
Overall Number of Participants Analyzed 39 37
Measure Type: Count of Participants
Unit of Measure: Participants
2
   5.1%
1
   2.7%
5.Secondary Outcome
Title Change in Rate of Cerebral Blood Flow in Subjects With Mild Cognitive Impairment MCI Treated With Atomoxetine / Inactive Compound Compared to Participants Treated With Inactive Compound / Atomoxetine
Hide Description Change in rate of cerebral blood flow is assessed by arterial spin labeling Magnetic Resonance Imaging (ASL-MRI) in subjects with Mild Cognitive Impairment MCI treated with Atomoxetine / Inactive Compound compared to participants treated with Inactive compound / Atomoxetine. The rates from the Baseline are compared to week 29 and week 55 among the participants treated with Atomoxetine / Inactive Compound compared to participants treated with Inactive compound / Atomoxetine. All MRIs will be reviewed by the investigators and the investigator.
Time Frame Baseline, Week 29 and Week 58
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Change in FluoroDeoxyGlucose (FDG) Uptake in Participants With Mild Cognitive Impairment (MCI) Treated With Atomoxetine / Inactive Compound Compared to Participants Treated With Inactive Compound / Atomoxetine
Hide Description Cerebral metabolic rate for glucose as measured by Fluoro Deoxy Glucose (FDG) uptake will be obtained by Positron Emission Tomography (PET) scan. The rates from the Baseline are compared to week 29 and week 55 among the subjects treated with Atomoxetine / Inactive Compound Compared to Participants Treated With Inactive Compound / Atomoxetine.
Time Frame Baseline, Week 29 and Week 58
Outcome Measure Data Not Reported
Time Frame All Adverse events were collected from Baseline to week 58 among the participants in both groups.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Atomoxetine Inactive Compound
Hide Arm/Group Description Participants in this arm included all the participants that received Atomoxetine, starting with 10 mg po daily and increasing weekly by increments to a maximum of 100 mg po daily or the maximum tolerated dose. The group includes 20 participants on Atomoxetine during period 1 and 19 participants on Atomoxetine during period 2. Participants in this arm included all the participants from both groups that received a matching placebo that have inactive compound. 19 participants on inactive compound during period 1 and 18 participants on inactive compound during period 2.
All-Cause Mortality
Atomoxetine Inactive Compound
Affected / at Risk (%) Affected / at Risk (%)
Total   0/39 (0.00%)      0/37 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Atomoxetine Inactive Compound
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/39 (12.82%)      1/37 (2.70%)    
Gastrointestinal disorders     
Appendicitis *  0/39 (0.00%)  0 1/37 (2.70%)  1
General disorders     
Hypothermia/dizziness *  1/39 (2.56%)  1 0/37 (0.00%)  0
Headache Pain *  1/39 (2.56%)  1 0/37 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Fracture of Right Leg/Hip (Pelvis) *  1/39 (2.56%)  1 0/37 (0.00%)  0
Nervous system disorders     
Dysautonomia *  1/39 (2.56%)  1 0/37 (0.00%)  0
Vascular disorders     
Severe Elevated Blood Pressure *  1/39 (2.56%)  1 0/37 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Atomoxetine Inactive Compound
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   39/39 (100.00%)      37/37 (100.00%)    
Gastrointestinal disorders     
Constipation *  4/39 (10.26%)  4 1/37 (2.70%)  1
Irritable Stomach *  11/39 (28.21%)  14 5/37 (13.51%)  5
General disorders     
Falls *  6/39 (15.38%)  7 2/37 (5.41%)  2
Dizziness *  9/39 (23.08%)  11 8/37 (21.62%)  8
Back Pain *  1/39 (2.56%)  1 3/37 (8.11%)  3
Loss of Appetite *  3/39 (7.69%)  3 0/37 (0.00%)  0
Dry Mouth *  10/39 (25.64%)  10 2/37 (5.41%)  2
Suicide *  2/39 (5.13%)  2 1/37 (2.70%)  1
Injury to Head and Ear *  1/39 (2.56%)  1 2/37 (5.41%)  2
Fatigue *  3/39 (7.69%)  3 3/37 (8.11%)  3
Body Cramps *  0/39 (0.00%)  0 2/37 (5.41%)  2
Metabolism and nutrition disorders     
Hypokalemia *  1/39 (2.56%)  1 2/37 (5.41%)  2
Musculoskeletal and connective tissue disorders     
Fracture *  2/39 (5.13%)  3 0/37 (0.00%)  0
Tremor *  3/39 (7.69%)  3 0/37 (0.00%)  0
Psychiatric disorders     
Anxiety *  2/39 (5.13%)  2 1/37 (2.70%)  1
Respiratory, thoracic and mediastinal disorders     
Upper respiratory infection *  4/39 (10.26%)  4 7/37 (18.92%)  8
Skin and subcutaneous tissue disorders     
Rash *  2/39 (5.13%)  2 2/37 (5.41%)  2
Vascular disorders     
Headache *  5/39 (12.82%)  7 2/37 (5.41%)  2
Hypertension *  2/39 (5.13%)  3 1/37 (2.70%)  2
*
Indicates events were collected by non-systematic assessment
Sample size is small leading to some analytical limitations
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Allan I. Levey, MD, PhD
Organization: Emory University
Phone: 404-727-7220
Responsible Party: Allan I Levey, MD, Emory University
ClinicalTrials.gov Identifier: NCT01522404     History of Changes
Other Study ID Numbers: IRB00054397
5U01AG010483 ( U.S. NIH Grant/Contract )
ATX-001 ( Other Identifier: Other )
First Submitted: January 25, 2012
First Posted: January 31, 2012
Results First Submitted: October 31, 2018
Results First Posted: December 5, 2018
Last Update Posted: December 5, 2018