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Trial of Rituximab for Graves' Ophthalmopathy

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ClinicalTrials.gov Identifier: NCT00595335
Recruitment Status : Completed
First Posted : January 16, 2008
Results First Posted : June 3, 2014
Last Update Posted : January 1, 2016
Sponsor:
Collaborators:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Center for Research Resources (NCRR)
Information provided by (Responsible Party):
Rebecca Bahn, Mayo Clinic

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Thyroid-associated Ophthalmopathy
Interventions Drug: Rituximab
Drug: Saline
Drug: Methylprednisolone
Enrollment 25

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Rituximab Placebo
Hide Arm/Group Description

Rituximab 1000 mg IV twice at 2-week intervals, each preceded by Methylprednisolone 100 mg IV as premedication to the rituximab infusion. All subjects will be treated with an acetaminophen tablet and a diphenhydramine hydrochloride tablet before the infusion.

Rituximab: Subjects will receive 2 infusions of rituximab (1000 mg IV), two weeks apart.

Methylprednisolone: Subjects will receive methylprednisolone 100 mg IV as premedication to the rituximab infusion.

Subjects will receive 2 infusions of saline IV, 2 weeks apart, each preceded by a premedication saline IV. All subjects will be treated with an acetaminophen tablet and a diphenhydramine hydrochloride tablet before the infusion.

Saline: Subjects will receive 2 infusions of saline IV, 2 weeks apart, each preceded by a premedication saline IV.

Period Title: Baseline to Six Months
Started 13 12
Completed 11 10
Not Completed 2 2
Reason Not Completed
Withdrawal by Subject             0             1
Disease Progression             1             1
Adverse Event             1             0
Period Title: Six Months to Twelve Months
Started 11 10
Completed 10 9
Not Completed 1 1
Reason Not Completed
Withdrawal by Subject             0             1
Disease Progression             1             0
Arm/Group Title Rituximab Placebo Total
Hide Arm/Group Description

Rituximab 1000 mg IV twice at 2-week intervals, each preceded by Methylprednisolone 100 mg IV as premedication to the rituximab infusion. All subjects will be treated with an acetaminophen tablet and a diphenhydramine hydrochloride tablet before the infusion.

Rituximab: Subjects will receive 2 infusions of rituximab (1000 mg IV), two weeks apart.

Methylprednisolone: Subjects will receive methylprednisolone 100 mg IV as premedication to the rituximab infusion.

Subjects will receive 2 infusions of saline IV, 2 weeks apart, each preceded by a premedication saline IV. All subjects will be treated with an acetaminophen tablet and a diphenhydramine hydrochloride tablet before the infusion.

Saline: Subjects will receive 2 infusions of saline IV, 2 weeks apart, each preceded by a premedication saline IV.

Total of all reporting groups
Overall Number of Baseline Participants 13 12 25
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 13 participants 12 participants 25 participants
57.6  (12.7) 61.8  (11.0) 58.6  (11.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 12 participants 25 participants
Female
9
  69.2%
8
  66.7%
17
  68.0%
Male
4
  30.8%
4
  33.3%
8
  32.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 13 participants 12 participants 25 participants
13 12 25
Clinical Activity Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 13 participants 12 participants 25 participants
4.9  (1.0) 5.3  (1.0) 5.1  (1.0)
[1]
Measure Description: The CAS, which is based on classical signs of inflammation (pain, redness, and swelling), consists of 7 equally weighted items. The total CAS (as used in this study) may range from 0 to 7. The higher the CAS, the greater degree of inflammation is present. A drop in CAS of 2 or more points suggests an improvement in the inflammatory components of the disease. A CAS ≥3 implies active disease.
1.Primary Outcome
Title Change in Clinical Activity Score (CAS)
Hide Description The clinical activity score (CAS), for Grave's ophthalmopathy has become a widely accepted tool to assess disease activity and help decide the management of the condition. The CAS, which is based on classical signs of inflammation (pain, redness, and swelling), consists of 7 equally weighted items. The total CAS (as used in this study) may range from 0 to 7. The higher the CAS, the greater degree of inflammation is present. A drop in CAS of 2 or more points suggests an improvement in the inflammatory components of the disease. A CAS ≥3 implies active disease.
Time Frame baseline, 6 months after the first infusion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Sample size was computed based on the expected drop of 2.9 and 1.5 points in the CAS score in rituximab and placebo groups. A sample size of 15 in each group will have 80% power to detect a difference in mean values of 1.4 assuming that the common standard deviation is 1.27 using a two group t-test with a 0.050 two-sided significance level.
Arm/Group Title Rituximab Placebo
Hide Arm/Group Description:

Rituximab 1000 mg IV twice at 2-week intervals, each preceded by Methylprednisolone 100 mg IV as premedication to the rituximab infusion. All subjects will be treated with an acetaminophen tablet and a diphenhydramine hydrochloride tablet before the infusion.

Rituximab: Subjects will receive 2 infusions of rituximab (1000 mg IV), two weeks apart.

Methylprednisolone: Subjects will receive methylprednisolone 100 mg IV as premedication to the rituximab infusion.

Subjects will receive 2 infusions of saline IV, 2 weeks apart, each preceded by a premedication saline IV. All subjects will be treated with an acetaminophen tablet and a diphenhydramine hydrochloride tablet before the infusion.

Saline: Subjects will receive 2 infusions of saline IV, 2 weeks apart, each preceded by a premedication saline IV.

Overall Number of Participants Analyzed 13 12
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.2  (2) -1.5  (1.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Placebo
Comments Comparison of the change between the two groups' CAS score at 6 months.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.73
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
2.Secondary Outcome
Title Failure Rate
Hide Description The failure rate was defined as a composite variable of CAS decrease of < 2 points or need for additional therapy (excluding cosmetic surgery) for the eye disease.
Time Frame 6 months after first infusion, 12 months after first infusion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was intent to treat. The last observation was carried forward from the subjects who dropped out before (or at) 24 weeks.
Arm/Group Title Rituximab Placebo
Hide Arm/Group Description:

Rituximab 1000 mg IV twice at 2-week intervals, each preceded by Methylprednisolone 100 mg IV as premedication to the rituximab infusion. All subjects will be treated with an acetaminophen tablet and a diphenhydramine hydrochloride tablet before the infusion.

Rituximab: Subjects will receive 2 infusions of rituximab (1000 mg IV), two weeks apart.

Methylprednisolone: Subjects will receive methylprednisolone 100 mg IV as premedication to the rituximab infusion.

Subjects will receive 2 infusions of saline IV, 2 weeks apart, each preceded by a premedication saline IV. All subjects will be treated with an acetaminophen tablet and a diphenhydramine hydrochloride tablet before the infusion.

Saline: Subjects will receive 2 infusions of saline IV, 2 weeks apart, each preceded by a premedication saline IV.

Overall Number of Participants Analyzed 13 12
Measure Type: Number
Unit of Measure: percentage of participants
Failure rate at 6 months 69 75
Failure rate at 12 months 46 50
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Placebo
Comments Comparison of the change between the two groups' failure rate at 6 months.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.75
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab, Placebo
Comments Comparison of the change between the two groups' failure rate at 12 months.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.85
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
3.Secondary Outcome
Title Change in Disease Severity
Hide Description Disease severity was measured by the NOSPECS Score. This classification scheme of the eye changes in thyroid eye disease was introduced by the American Thyroid Association. It separates patients into seven classes of disease (class 0–6), with 0 being no signs or symptoms and 6 being sight loss. (The acronym is based on the first letter of the defining characteristic of each class, the classification is known as: ‘no signs or symptoms; only signs; soft tissue; proptosis; extraocular muscle; cornea; sight loss’ (NOSPECS) ).
Time Frame baseline, 6 months after first infusion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intention to treat analysis
Arm/Group Title Rituximab Placebo
Hide Arm/Group Description:

Rituximab 1000 mg IV twice at 2-week intervals, each preceded by Methylprednisolone 100 mg IV as premedication to the rituximab infusion.

Rituximab: Subjects will receive 2 infusions of rituximab (1000 mg IV), two weeks apart.

Methylprednisolone: Subjects will receive methylprednisolone 100 mg IV as premedication to the rituximab infusion.

Subjects will receive 2 infusions of saline IV, 2 weeks apart, each preceded by a premedication saline IV.

Saline: Subjects will receive 2 infusions of saline IV, 2 weeks apart, each preceded by a premedication saline IV.

Overall Number of Participants Analyzed 13 12
Measure Type: Number
Unit of Measure: participants
Improvement by 1 class 6 8
Improvement by 2 classes 2 2
Deterioration 2 0
No change 3 2
4.Secondary Outcome
Title Change in Proptosis
Hide Description Eye proptosis is a condition resulting in forward displacement of the globe from its normal position within the orbit. It is measured by computed tomography. Improvement in proptosis was defined as a decrease in proptosis by ≥2 mm.
Time Frame baseline, 12 months after first infusion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Rituximab Placebo
Hide Arm/Group Description:

Rituximab 1000 mg IV twice at 2-week intervals, each preceded by Methylprednisolone 100 mg IV as premedication to the rituximab infusion.

Rituximab: Subjects will receive 2 infusions of rituximab (1000 mg IV), two weeks apart.

Methylprednisolone: Subjects will receive methylprednisolone 100 mg IV as premedication to the rituximab infusion.

Subjects will receive 2 infusions of saline IV, 2 weeks apart, each preceded by a premedication saline IV.

Saline: Subjects will receive 2 infusions of saline IV, 2 weeks apart, each preceded by a premedication saline IV.

Overall Number of Participants Analyzed 13 12
Mean (Standard Deviation)
Unit of Measure: mm
Proptosis right eye 0.82  (1.4) 0.80  (1.3)
Proptosis left eye 0.1  (1.2) 0.0  (1.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Placebo
Comments Comparison of the change between the two groups in proptosis in the right eye at 12 months.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.97
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab, Placebo
Comments Comparison of the change between the two groups in change in proptosis in left eye at 12 months.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.86
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
5.Secondary Outcome
Title Change in Lid Fissure
Hide Description

The palpebral fissure is the elliptic space between the medial and lateral canthi of the two open eye lids. In adults, this measures about 10mm vertically and 30mm horizontally. The fissure may be increased in vertical height in Graves' disease.

Improvement was defined as a decrease in lid aperture width by ≥3 mm.

Time Frame baseline, 6 months after first infusion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intention to treat analysis
Arm/Group Title Rituximab Placebo
Hide Arm/Group Description:

Rituximab 1000 mg IV twice at 2-week intervals, each preceded by Methylprednisolone 100 mg IV as premedication to the rituximab infusion.

Rituximab: Subjects will receive 2 infusions of rituximab (1000 mg IV), two weeks apart.

Methylprednisolone: Subjects will receive methylprednisolone 100 mg IV as premedication to the rituximab infusion.

Subjects will receive 2 infusions of saline IV, 2 weeks apart, each preceded by a premedication saline IV.

Saline: Subjects will receive 2 infusions of saline IV, 2 weeks apart, each preceded by a premedication saline IV.

Overall Number of Participants Analyzed 13 12
Median (Inter-Quartile Range)
Unit of Measure: mm
Lid fissure right eye
0
(-1 to 1)
0
(-1 to 1)
Lid fissure left eye
0
(-1.5 to 1)
0.5
(-1 to 1.75)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Placebo
Comments Comparison of the change in lid fissure in the right eye between the two groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.98
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab, Placebo
Comments Comparison of the change in lid fissure in the left eye between the two groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.49
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
6.Secondary Outcome
Title Change in Extraocular Motility
Hide Description

Change extraocular motility was assessed using the Gorman diplopia score. Diplopia, commonly known as double vision, is the simultaneous perception of two images of a single object that may be displaced horizontally, vertically, or diagonally (i.e., both vertically and horizontally) in relation to each other. It is usually the result of impaired function of the extraocular muscles, where both eyes are still functional but they cannot converge to target the desired object.

The Gorman diplopia score includes four categories: 1) no diplopia (absent), 2) diplopia when the patient is tired or awakening (intermittent), 3) diplopia at extremes of gaze (inconstant), and 4) continuous diplopia in the primary or reading position (constant).

Time Frame baseline, 6 months after first infusion, 12 months after first infusion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intention to treat analysis
Arm/Group Title Rituximab Placebo
Hide Arm/Group Description:

Rituximab 1000 mg IV twice at 2-week intervals, each preceded by Methylprednisolone 100 mg IV as premedication to the rituximab infusion.

Rituximab: Subjects will receive 2 infusions of rituximab (1000 mg IV), two weeks apart.

Methylprednisolone: Subjects will receive methylprednisolone 100 mg IV as premedication to the rituximab infusion.

Subjects will receive 2 infusions of saline IV, 2 weeks apart, each preceded by a premedication saline IV.

Saline: Subjects will receive 2 infusions of saline IV, 2 weeks apart, each preceded by a premedication saline IV.

Overall Number of Participants Analyzed 13 12
Median (Inter-Quartile Range)
Unit of Measure: units on a scale
Change baseline-6 months
3
(2 to 3.5)
2.5
(0 to 4)
Change baseline-12 months
2
(0.75 to 3.25)
1.5
(0.75 to 3.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Placebo
Comments Comparison of change between groups in extraocular motility at 6 months.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.21
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab, Placebo
Comments Comparison of change between groups in extraocular motility at 12 months.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.64
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
7.Secondary Outcome
Title Graves' Ophthalmopathy Quality of Life Score Using the Short Form-12 (SF-12) Health Survey
Hide Description Quality of life (QoL) was measured by the SF-12 questionnaire. The SF-12 is a multipurpose short form survey with 12 questions, all selected from the SF-36 Health Survey. Physical and Mental Health Composite Scores are computed (combined, scored, and weighted) using the scores of the 12 questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. Improvement was defined as a change of ≥ 6 points.
Time Frame baseline, 6 months after first infusion, 12 months after first infusion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Rituximab Placebo
Hide Arm/Group Description:

Rituximab 1000 mg IV twice at 2-week intervals, each preceded by Methylprednisolone 100 mg IV as premedication to the rituximab infusion.

Rituximab: Subjects will receive 2 infusions of rituximab (1000 mg IV), two weeks apart.

Methylprednisolone: Subjects will receive methylprednisolone 100 mg IV as premedication to the rituximab infusion.

Subjects will receive 2 infusions of saline IV, 2 weeks apart, each preceded by a premedication saline IV.

Saline: Subjects will receive 2 infusions of saline IV, 2 weeks apart, each preceded by a premedication saline IV.

Overall Number of Participants Analyzed 13 12
Median (Inter-Quartile Range)
Unit of Measure: units on a scale
Baseline QoL physical
53.2
(42.1 to 56.7)
39.9
(33.5 to 48.8)
Baseline QoL mental
44.3
(32.8 to 50.7)
46.1
(36 to 51.3)
6 months QoL physical
45.9
(43.6 to 50.8)
40.3
(38.5 to 52.1)
6 months QoL mental
52.8
(36.1 to 56.7)
46.1
(35.4 to 57.4)
12 months QoL physical
51.8
(49.8 to 55.5)
46.7
(41.1 to 53.6)
12 months QoL mental
56.1
(42.8 to 57.8)
49.4
(35.4 to 56.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Placebo
Comments Comparison of the arms for QoL SF-12 physical score at 6 months.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.36
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab, Placebo
Comments Comparison of the arms for QoL SF-12 mental score at 6 months.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.91
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rituximab, Placebo
Comments Comparison of the arms for QoL SF-12 physical score at 12 months.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.29
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Rituximab, Placebo
Comments Comparison of the arms for QoL SF-12 mental score at 12 months.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.18
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
8.Secondary Outcome
Title Failure Rate at One Year
Hide Description The failure rate was defined as a composite variable of CAS decrease of < 2 points or need for additional therapy (excluding cosmetic surgery) for the eye disease.
Time Frame one year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was intent to treat. The last observation was carried forward from the subjects who dropped out before (or at) 52 weeks.
Arm/Group Title Rituximab Placebo
Hide Arm/Group Description:
Rituximab 1000 mg IV twice at 2-week intervals, each preceded by Methylprednisolone 100 mg IV as premedication to the rituximab infusion. All subjects will be treated with an acetaminophen tablet and a diphenhydramine hydrochloride tablet before the infusion.
Subjects will receive 2 infusions of saline IV, 2 weeks apart, each preceded by a premedication saline IV. All subjects will be treated with an acetaminophen tablet and a diphenhydramine hydrochloride tablet before the infusion.
Overall Number of Participants Analyzed 13 12
Measure Type: Number
Unit of Measure: percentage of participants
46 50
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Placebo
Comments Comparison of the change between the two groups' failure rate at 12 months.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.85
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Time Frame Participants were followed for adverse events for one year after the first infusion.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Rituximab Placebo
Hide Arm/Group Description

Rituximab 1000 mg IV twice at 2-week intervals, each preceded by Methylprednisolone 100 mg IV as premedication to the rituximab infusion. All subjects will be treated with an acetaminophen tablet and a diphenhydramine hydrochloride tablet before the infusion.

Rituximab: Subjects will receive 2 infusions of rituximab (1000 mg IV), two weeks apart.

Methylprednisolone: Subjects will receive methylprednisolone 100 mg IV as premedication to the rituximab infusion.

Subjects will receive 2 infusions of saline IV, 2 weeks apart, each preceded by a premedication saline IV. All subjects will be treated with an acetaminophen tablet and a diphenhydramine hydrochloride tablet before the infusion.

Saline: Subjects will receive 2 infusions of saline IV, 2 weeks apart, each preceded by a premedication saline IV.

All-Cause Mortality
Rituximab Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Rituximab Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/13 (15.38%)      0/12 (0.00%)    
Eye disorders     
Dysthroid optic neuropathy   2/13 (15.38%)  2 0/12 (0.00%)  0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Rituximab Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/13 (46.15%)      3/12 (25.00%)    
Blood and lymphatic system disorders     
Vasculitis legs   1/13 (7.69%)  1 0/12 (0.00%)  0
Eye disorders     
Significant eye tearing   1/13 (7.69%)  1 0/12 (0.00%)  0
Gastrointestinal disorders     
Tongue pain   1/13 (7.69%)  1 0/12 (0.00%)  0
Indigestion   1/13 (7.69%)  1 0/12 (0.00%)  0
Abdominal Discomfort   0/13 (0.00%)  0 1/12 (8.33%)  2
Diarrhea   0/13 (0.00%)  0 1/12 (8.33%)  1
Infections and infestations     
Left eye conjunctivitis   0/13 (0.00%)  0 1/12 (8.33%)  1
Musculoskeletal and connective tissue disorders     
Myalgia   0/13 (0.00%)  0 2/12 (16.67%)  2
Arthritis of left hip   1/13 (7.69%)  1 0/12 (0.00%)  0
Arthralgia both knees   1/13 (7.69%)  1 0/12 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Acute Bronchitis   1/13 (7.69%)  1 0/12 (0.00%)  0
Skin and subcutaneous tissue disorders     
Rash on face   1/13 (7.69%)  1 0/12 (0.00%)  0
Itching of face and scalp   1/13 (7.69%)  1 0/12 (0.00%)  0
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr. Rebecca S. Bahn
Organization: Mayo Clinic
Phone: 507-284-2462
Responsible Party: Rebecca Bahn, Mayo Clinic
ClinicalTrials.gov Identifier: NCT00595335     History of Changes
Other Study ID Numbers: 06-006130
R01DK077814-01 ( U.S. NIH Grant/Contract )
UL1RR024150 ( U.S. NIH Grant/Contract )
First Submitted: January 1, 2008
First Posted: January 16, 2008
Results First Submitted: March 26, 2014
Results First Posted: June 3, 2014
Last Update Posted: January 1, 2016