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CEP-1 Hormonal Regulation of Circulating Endothelial Progenitor Cells and HDL-C in Men (CEP-1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00729859
Recruitment Status : Completed
First Posted : August 8, 2008
Results First Posted : October 12, 2012
Last Update Posted : October 12, 2012
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Stephanie T. Page, University of Washington

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Participant);   Primary Purpose: Prevention
Condition Healthy
Interventions Drug: Acyline
Drug: Acyline + Testosterone gel
Drug: Acyline + testosterone gel + anastrozole
Enrollment 31
Recruitment Details Subjects were recruited using rosters from prior research studies, newspaper and online advertisements. Recruitment began December 2008 and ended March 2010.
Pre-assignment Details

Before study procedures,2 withdrew consent and 1 was withdrawn by the investigator for missing appointments.4 failed inclusion criteria(1-anemia,1-low testosterone,1-high BMI,1-medications.

31 men enrolled. 22 men completed.

Arm/Group Title Group 1: Acyline + Placebo Gel, Placebo Pill Group 2: Acyline, Testosterone Gel, Placebo Pill Group 3: Acyline, Testosterone Gel, Anastrazole Pill
Hide Arm/Group Description Acyline 300 µg/kg injections Day 0 & 14 + placebo (no active ingredients) transdermal gel daily for 28 days + oral placebo daily for 28 days Acyline 300 µg/kg injections Day 0 & 14 + Testosterone gel (Testim) 10g 1% daily for 28 days + oral placebo daily for 28 days Acyline 300 μg/kg injections Day 0 & 14 + 1% Testosterone gel 10g transdermal daily for 28 days + oral anastrozole 1 mg (Arimidex) daily for 28 days
Period Title: Overall Study
Started 8 8 8
Completed 8 6 8
Not Completed 0 2 0
Reason Not Completed
Adverse Event             0             1             0
Withdrawal by Subject             0             1             0
Arm/Group Title Group 1: Acyline + Placebo Gel, Placebo Pill Group 2: Acyline, Testosterone Gel, Placebo Pill Group 3: Acyline, Testosterone Gel, Anastrazole Pill Total
Hide Arm/Group Description Acyline 300 µg/kg injections Day 0 & 14 + placebo (no active ingredients) transdermal gel daily for 28 days + oral placebo daily for 28 days Acyline 300 µg/kg injections Day 0 & 14 + Testosterone gel (Testim) 10g 1% daily for 28 days + oral placebo daily for 28 days Acyline 300 μg/kg injections Day 0 & 14 + 1% Testosterone gel 10g transdermal daily for 28 days + oral anastrozole 1 mg (Arimidex) daily for 28 days Total of all reporting groups
Overall Number of Baseline Participants 8 8 8 24
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 8 participants 8 participants 24 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
8
 100.0%
8
 100.0%
8
 100.0%
24
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 8 participants 8 participants 8 participants 24 participants
38.5  (10.6) 24.3  (4.0) 25.8  (8.4) 30.0  (10.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 8 participants 8 participants 24 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
8
 100.0%
8
 100.0%
8
 100.0%
24
 100.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 8 participants 8 participants 24 participants
Hispanic or Latino
0
   0.0%
1
  12.5%
1
  12.5%
2
   8.3%
Not Hispanic or Latino
8
 100.0%
7
  87.5%
7
  87.5%
22
  91.7%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 8 participants 8 participants 24 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
2
  25.0%
1
  12.5%
3
  12.5%
White
8
 100.0%
6
  75.0%
7
  87.5%
21
  87.5%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 8 participants 8 participants 8 participants 24 participants
26.2  (2.5) 27.1  (3.8) 23.7  (2.1) 25.5  (3.0)
1.Primary Outcome
Title Endothelial Progenitor Cells
Hide Description Number of CD33 + CD134+ cells as a percentage of all lymphocytes
Time Frame Baseline, Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Statistical analyses were limited to changes from baseline within a given group and between-group comparisons were not performed
Arm/Group Title Group 1: Acyline + Placebo Gel + Placebo Pill Group 2: Acyline + T-gel 10g/Day + Placebo Pill Group 3: Acyline + T-gel + Oral Anastrozole 1mg
Hide Arm/Group Description:
Group 1: Acyline injections, transdermal placebo gel 10 g/day for 28 days, oral daily placebo pill for 28 days
Acyline SQ inj. Day 0 & 14 + T-gel and placebo pill for 28 days
Acyline SQ inj. Day 0 & 14 + T-gel and anastrozole for 28 days
Overall Number of Participants Analyzed 8 0 0
Mean (Standard Deviation)
Unit of Measure: percentage of all lymphocytes
Baseline 0.101  (0.032)
Day 28 0.081  (0.040)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: Acyline + Placebo Gel + Placebo Pill
Comments p value for the difference = 0.28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.28
Comments [Not Specified]
Method paired t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
0.005 to 0.035
Parameter Dispersion
Type: Standard Deviation
Value: 0.0075
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Follicle Stimulating Hormone (FSH)
Hide Description [Not Specified]
Time Frame Baseline, 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol, the first 8 subjects were assigned to Group 1. Subsequent subjects were randomly assigned to Group 2 or Group 3.
Arm/Group Title Group 1: Acyline + Placebo Gel, Placebo Pill Group 2: Acyline, Testosterone Gel Group 3: Acyline, Testosterone Gel, Anastrazole Pill
Hide Arm/Group Description:
Group 1: Acyline injections, transdermal placebo gel 10 g/day for 28 days, oral daily placebo pill for 28 days
Group 2: Acyline injections, transdermal testosterone gel 10 g/day for 28 days, oral daily placebo pill for 28 days
Arm 3: Acyline injections, transdermal testosterone gel 10 g/day for 28 days, oral daily anastrazole pill 1 mg for 28 days
Overall Number of Participants Analyzed 8 6 8
Mean (Standard Deviation)
Unit of Measure: IU/L
Baseline 4.2  (2.4) 2.9  (1.3) 2.5  (0.9)
Day 28 0.42  (0.7) 0.39  (0.5) 0.87  (0.8)
3.Secondary Outcome
Title Luteinizing Hormone Concentration (LH)
Hide Description [Not Specified]
Time Frame Baseline, Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was per protocol. Following screening, the first 8 subjects were assigned to group I, and subsequent subjects enrolled were randomly assigned to either group 2 or 3.
Arm/Group Title Group 1: Acyline + Placebo Gel, Placebo Pill Group 2: Acyline, Testosterone Gel Group 3: Acyline, Testosterone Gel, Anastrozole
Hide Arm/Group Description:
Group 1: Acyline injections, transdermal placebo gel 10 g/day for 28 days, oral daily placebo pill for 28 days
Group 2: Acyline injections, transdermal testosterone gel 10 g/day for 28 days, oral daily placebo pill for 28 days
Arm 3: Acyline injections, transdermal testosterone gel 10 g/day for 28 days, oral daily anastrozole pill 1 mg for 28 days.
Overall Number of Participants Analyzed 8 6 8
Mean (Standard Deviation)
Unit of Measure: IU/L
Baseline 4.3  (2.3) 4.7  (1.9) 4.4  (2.2)
Day 28 0.31  (0.2) 0.69  (1.2) 1.55  (1.6)
4.Secondary Outcome
Title Testosterone Concentration
Hide Description [Not Specified]
Time Frame Baseline, Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol, the first 8 subjects were assigned to group I. Subsequent subjects were randomized to group 2 or group 3.
Arm/Group Title Group 1: Acyline + Placebo Gel, Placebo Pill Group 2: Acyline, Testosterone Gel Group 3: Acyline, Testosterone Gel, Anastrozole
Hide Arm/Group Description:
Group 1: Acyline injections, transdermal placebo gel 10 g/day for 28 days, oral daily placebo pill for 28 days
Group 2: Acyline injections, transdermal testosterone gel 10 g/day for 28 days, oral daily placebo pill for 28 days
Group 3: Acyline injections, transdermal testosterone gel 10 g/day for 28 days, oral daily anastrozole pill 1 mg for 28 days.
Overall Number of Participants Analyzed 8 6 8
Mean (Standard Deviation)
Unit of Measure: nmol/L
Baseline testosterone concentration 15.4  (3.4) 16.3  (3.3) 16.5  (2.6)
Day 28 testosterone concentration 0.8  (0.8) 17.8  (5.5) 19.0  (7.3)
5.Secondary Outcome
Title Estradiol Concentration
Hide Description [Not Specified]
Time Frame Baseline, Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol, the first 8 subjects were assigned to Group 1. Subsequent subjects were randomly assigned to Group 2 or Group 3.
Arm/Group Title Group 1: Acyline + Placebo Gel, Placebo Pill Group 2: Acyline, Testosterone Gel Group 3: Acyline, Testosterone Gel, Anastrozole Pill
Hide Arm/Group Description:
Group 1: Acyline injections, transdermal placebo gel 10 g/day for 28 days, oral daily placebo pill for 28 days
Group 2: Acyline injections, transdermal testosterone gel 10 g/day for 28 days, oral daily placebo pill for 28 days
Group 3: Acyline injections, transdermal testosterone gel 10 g/day for 28 days, oral daily anastrozole pill 1 mg for 28 days.
Overall Number of Participants Analyzed 8 6 8
Mean (Standard Deviation)
Unit of Measure: pmol/L
Baseline 95.4  (18.2) 117.8  (28.6) 96.3  (21.9)
Day 28 31.9  (11.2) 109.0  (28.8) 36.5  (14.3)
6.Secondary Outcome
Title Sex Hormone Binding Globulin (SHBG)
Hide Description [Not Specified]
Time Frame Baseline, Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol, the first 8 subjects were assigned to Group I. Subsequent subjects were randomly assigned to Group 2 or Group 3.
Arm/Group Title Group 1: Acyline + Placebo Gel, Placebo Pill Group 2: Acyline, Testosterone Gel Group 3: Acyline, Testosterone Gel, Anastrozole Pill
Hide Arm/Group Description:
Group 1: Acyline injections, transdermal placebo gel 10 g/day for 28 days, oral daily placebo pill for 28 days
Group 2: Acyline injections, transdermal testosterone gel 10 g/day for 28 days, oral daily placebo pill for 28 days
Group 3: Acyline injections, transdermal testosterone gel 10 g/day for 28 days, oral daily anastrozole pill 1 mg for 28 days.
Overall Number of Participants Analyzed 8 6 8
Mean (Standard Deviation)
Unit of Measure: nmol/L
Baseline 34.9  (17.1) 23.0  (10.9) 27.6  (6.3)
Day 28 37.5  (16.4) 22.1  (10.1) 25.1  (4.7)
7.Secondary Outcome
Title Quantitative Insulin Sensitivity Check Index (QUICKI)
Hide Description QUICKI is a measure of insulin sensitivity calculated using fasting insulin and glucose concentration in a participants blood. Higher QUICKI are associated with decreased insulin resistance and increased insulin sensitivity.
Time Frame Baseline, Day 28, Day 56
Hide Outcome Measure Data
Hide Analysis Population Description
per protocol
Arm/Group Title Group 1: Acyline + Placebo Gel, Placebo Pill Group 2: Acyline, Testosterone Gel, Placebo Pill Group 3: Acyline, Testosterone Gel, Oral Anastrozole
Hide Arm/Group Description:
Group 1: Acyline injections, transdermal placebo gel 10 g/day for 28 days, oral daily placebo pill for 28 days
Group 2: Acyline injections, transdermal testosterone gel 10 g/day for 28 days, oral daily placebo pill for 28 days
Group 3: Acyline injections, transdermal testosterone gel 10 g/day for 28 days, oral daily anastrozole pill 1 mg for 28 days.
Overall Number of Participants Analyzed 8 6 8
Mean (Standard Deviation)
Unit of Measure: QUICKI index
Baseline 0.36  (0.03) 0.35  (0.02) 0.36  (0.02)
Day 28 0.34  (0.03) 0.35  (0.02) 0.38  (0.02)
Day 56 0.35  (0.03) 0.35  (0.02) 0.36  (0.02)
8.Secondary Outcome
Title Homeostasis Model of Insulin Resistance (HOMA-IR)
Hide Description HOMA IR is a measure of insulin sensitivity calculated using fasting insulin and glucose concentration in a participants blood. Higher HOMA IR numbers are associated with increased insulin resistance and decreased insulin sensitivity.
Time Frame Baseline, Day 28, Day 56
Hide Outcome Measure Data
Hide Analysis Population Description
per protocol
Arm/Group Title Group 1: Acyline + Placebo Gel, Placebo Pill Group 2: Acyline, Testosterone Gel, Placebo Pill Group 3: Acyline, Testosterone Gel, Oral Anastrozole
Hide Arm/Group Description:
Group 1: Acyline injections, transdermal placebo gel 10 g/day for 28 days, oral daily placebo pill for 28 days
Group 2: Acyline injections, transdermal testosterone gel 10 g/day for 28 days, oral daily placebo pill for 28 days
Group 3: Acyline injections, transdermal testosterone gel 10 g/day for 28 days, oral daily anastrozole pill 1 mg for 28 days.
Overall Number of Participants Analyzed 8 6 8
Mean (Standard Deviation)
Unit of Measure: HOMA score
Baseline 1.8  (0.9) 2.0  (0.9) 1.6  (0.6)
Day 28 2.4  (1.0) 1.9  (0.9) 1.4  (0.8)
Day 56 2.2  (0.9) 1.9  (0.9) 1.7  (0.8)
9.Secondary Outcome
Title Fasting Serum Insulin
Hide Description [Not Specified]
Time Frame Baseline, Day 28, Day 56
Hide Outcome Measure Data
Hide Analysis Population Description
per protocol
Arm/Group Title Group 1: Acyline + Placebo Gel, Placebo Pill Group 2: Acyline, Testosterone Gel, Placebo Pill Group 3: Acyline, Testosterone Gel, Oral Anastrozole
Hide Arm/Group Description:
Group 1: Acyline injections, transdermal placebo gel 10 g/day for 28 days, oral daily placebo pill for 28 days
Group 2: Acyline injections, transdermal testosterone gel 10 g/day for 28 days, oral daily placebo pill for 28 days
Group 3: Acyline injections, transdermal testosterone gel 10 g/day for 28 days, oral daily anastrozole pill 1 mg for 28 days.
Overall Number of Participants Analyzed 8 6 8
Mean (Standard Deviation)
Unit of Measure: picomolar
Baseline 54  (26) 65  (28) 50  (16)
Day 28 69  (25) 59  (26) 42  (23)
Day 56 54  (26) 64  (27) 50  (16)
10.Secondary Outcome
Title Fasting Lipid Levels
Hide Description [Not Specified]
Time Frame Baseline, Day 28, Day 56
Hide Outcome Measure Data
Hide Analysis Population Description
per protocol
Arm/Group Title Group 1: Acyline + Placebo Gel, Placebo Pill Group 2: Acyline, Testosterone Gel, Placebo Pill Group 3: Acyline, Testosterone Gel, Oral Anastrozole
Hide Arm/Group Description:
Group 1: Acyline injections, transdermal placebo gel 10 g/day for 28 days, oral daily placebo pill for 28 days
Group 2: Acyline injections, transdermal testosterone gel 10 g/day for 28 days, oral daily placebo pill for 28 days
Group 3: Acyline injections, transdermal testosterone gel 10 g/day for 28 days, oral daily anastrozole pill 1 mg for 28 days.
Overall Number of Participants Analyzed 8 6 8
Mean (Standard Deviation)
Unit of Measure: mmol/L
Total cholesterol Day 0 4.97  (1.1) 4.48  (0.4) 4.56  (1.5)
Total cholesterol Day 28 5.44  (1.2) 4.51  (0.3) 4.56  (0.9)
Total cholesterol Day 56 4.95  (1.1) 4.14  (0.6) 4.27  (1.2)
LDL choesterol Day 0 2.95  (0.8) 2.77  (0.3) 2.67  (1.3)
LDL cholesterol Day 28 3.29  (0.7) 2.80  (0.2) 2.75  (0.8)
LDL cholesterol Day 56 2.87  (0.5) 2.49  (0.5) 2.51  (1.0)
HDL cholesterol Day 0 1.19  (0.2) 1.32  (0.2) 1.40  (0.2)
HDL cholesterol Day 28 1.37  (0.2) 1.32  (0.1) 1.32  (0.2)
HDL cholesterol Day 56 1.19  (0.2) 1.32  (0.2) 1.30  (0.2)
Triglycerides Day 0 1.79  (2.1) 0.82  (0.2) 1.08  (0.5)
Triglycerides Day 28 1.73  (1.4) 0.86  (0.3) 1.08  (0.4)
Triglycerides Day 56 1.89  (2.3) 0.80  (0.4) 1.02  (0.3)
Time Frame Dec 2008 - May 2010
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Group 1: Acyline + Placebo Gel, Placebo Pill Group 2: Acyline, Testosterone Gel, Placebo Pill Group 3: Acyline, Testosterone Gel, Anastrazole Pill
Hide Arm/Group Description Acyline 300 µg/kg injections Day 0 & 14 + placebo (no active ingredients) transdermal gel daily for 28 days + oral placebo daily for 28 days Acyline 300 µg/kg injections Day 0 & 14 + Testosterone gel (Testim) 10g 1% daily for 28 days + oral placebo daily for 28 days Acyline 300 μg/kg injections Day 0 & 14 + 1% Testosterone gel 10g transdermal daily for 28 days + oral anastrozole 1 mg (Arimidex) daily for 28 days
All-Cause Mortality
Group 1: Acyline + Placebo Gel, Placebo Pill Group 2: Acyline, Testosterone Gel, Placebo Pill Group 3: Acyline, Testosterone Gel, Anastrazole Pill
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Group 1: Acyline + Placebo Gel, Placebo Pill Group 2: Acyline, Testosterone Gel, Placebo Pill Group 3: Acyline, Testosterone Gel, Anastrazole Pill
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/8 (0.00%)      0/6 (0.00%)      0/8 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Group 1: Acyline + Placebo Gel, Placebo Pill Group 2: Acyline, Testosterone Gel, Placebo Pill Group 3: Acyline, Testosterone Gel, Anastrazole Pill
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/8 (75.00%)      1/6 (16.67%)      2/8 (25.00%)    
Endocrine disorders       
emotional lability, irritability  [1]  1/8 (12.50%)  1 0/6 (0.00%)  0 1/8 (12.50%)  1
fatigue  [2]  2/8 (25.00%)  2 1/6 (16.67%)  1 0/8 (0.00%)  0
hot flashes  [3]  3/8 (37.50%)  3 0/6 (0.00%)  0 0/8 (0.00%)  0
lightheadedness, clammy  [4]  1/8 (12.50%)  1 0/6 (0.00%)  0 0/8 (0.00%)  0
low libido  [5]  4/8 (50.00%)  4 0/6 (0.00%)  0 1/8 (12.50%)  1
Skin and subcutaneous tissue disorders       
itching at acyline site  [6]  1/8 (12.50%)  1 1/6 (16.67%)  1 0/8 (0.00%)  0
skin irritation, gel application site  [7]  1/8 (12.50%)  1 0/6 (0.00%)  0 1/8 (12.50%)  1
itching rash   1/8 (12.50%)  1 0/6 (0.00%)  0 0/8 (0.00%)  0
Indicates events were collected by systematic assessment
[1]
This is expected in group 1 subjects (hypogonadal). The group 3 subject with emotional lability also reported skin irritation at the testosterone gel site.
[2]
Fatigue is anticipated and consistent with hypogonadal symptoms for Group 1 (placebo gel. The group 2 subject also reported studying late and spending the night in the library during midterm week. Fatigue is described in the consent as a possibility.
[3]
Hot flashes are anticipated and consistent with hypogonadal symptoms for Group 1 (placebo gel). This is described in the consent.
[4]
Mild symptoms occurred two days and were deemed possibly related to the drug. No action or medications were required in this group I (hypogonadal symptoms expected) subject.
[5]
Low libido is anticipated and consistent with hypogonadal symptoms for Group 1 (placebo gel). This is described in the consent.
[6]
The written consent describes itchiness at the site in most men. One (group 2)is not counted here, but is described in "participant flow". Symptoms had resolved on Day 14 but he withdrew consent before the second acyline injection.
[7]
One(group 1) complaint of itchiness;one(group 3) complaint of dry skin at testosterone gel application site. Both subjects were instructed to apply elsewhere; complaints were resolved with no further symptoms at old and new application sites.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Stephanie T. Page, MD, PhD
Organization: University of Washington
Phone: 206-616-0483
EMail: page@u.washington.edu
Other Publications:
Layout table for additonal information
Responsible Party: Stephanie T. Page, University of Washington
ClinicalTrials.gov Identifier: NCT00729859     History of Changes
Other Study ID Numbers: 33853-A
U54HD042454 ( U.S. NIH Grant/Contract )
First Submitted: August 5, 2008
First Posted: August 8, 2008
Results First Submitted: June 2, 2011
Results First Posted: October 12, 2012
Last Update Posted: October 12, 2012