AMDB1: Infliximab, Sirolimus and Daclizumab to Treat Age-Related Macular Degeneration
Study Details
Study Description
Brief Summary
This study examined whether the anti-inflammatory medicines infliximab, sirolimus or daclizumab, when given with a participant's current therapies, would prevent the growth of new blood vessels in the eye in participants with age-related macular degeneration (AMD).
Participants 55 years of age and older with AMD and drusen larger than 63um may be eligible for this study. Vision in the study eye was between 20/20 and 20/400.
Participants were randomly assigned to one of three treatments - infliximab, sirolimus, or daclizumab - or to observation only. In addition, participants may have been treated by their ophthalmologist as needed for their AMD.
Infliximab and daclizumab were given intravenously (through a vein); infusions were given at enrollment in the study, then at 2 weeks, and then monthly.
Sirolimus was a pill that was taken every other day for the duration of the study. At 6 months, participants were evaluated to see whether continuing treatment would be beneficial.
In addition to treatment or observation, participants underwent the following procedures:
Physical examination at enrollment and 6 months.
Photographs of the back of the eye, fluorescein angiography, indocyanine green angiography and measurement of retinal thickness at enrollment and months 1, 3 and 6.
-
Fluorescein angiography evaluated the eye's blood vessels. A yellow dye was injected into an arm vein and traveled to the blood vessels in the eyes. Pictures of the retina were taken using a camera that flashed a blue light into the eye. The pictures show if any dye has leaked from the vessels into the retina, indicating possible blood vessel abnormality.
-
Indocyanine green angiography identified feeder vessels that may have supplied abnormal blood vessels. This procedure is similar to fluorescein angiography, but uses a green dye and flashes an invisible light.
-
Optical coherence tomography measures retinal thickness. This test shines a light into the eye and produces cross-sectional pictures of the retina. These measurements are repeated during the study to determine whether retinal thickening is getting better or worse, or staying the same.
Tuberculin skin test and chest x-ray at enrollment and 6 months.
Blood tests at enrollment and months 1, 3 and 6.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
There has been much interest in the possible role of the immune system in AMD. Experimental models and patient material have, to date, suggested a role for macrophages and complement. This study hypothesized that the underlying mechanism that leads to choroidal neovascularization (CNV) is similar to those at play in atherosclerosis. If this is the case, the investigators believed that CNV treatment should be amenable to new immunomodulatory agents directed against specific parts of the immune system.
After therapy with anti-angiogenic agents not leading to a persistent remission of CNV due to AMD, participants were treated with one of three immunomodulatory agents or were observed in conjunction with their continued anti-angiogenic therapy. Thus the participant continued with the anti-angiogenic therapy they received after randomization. The investigators hypothesized that this combination therapy would inhibit progression of CNV associated with AMD.
This was an open-label, phase II, randomized, single center clinical trial of 18 study participants randomized to receive one of three immunomodulatory agents or was observed in conjunction with their anti-angiogenic therapy.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Intravenous Daclizumab Participants randomly assigned to intravenous (IV) daclizumab received 8 mg/kg of IV daclizumab at baseline, then 4 mg/kg of IV daclizumab at Week 2 and then 2 mg/kg of IV daclizumab monthly for the rest of the 6-month study. |
Drug: Intravenous Daclizumab
Participants randomly assigned to intravenous (IV) daclizumab received 8 mg/kg of IV daclizumab at baseline, then 4 mg/kg of IV daclizumab at Week 2 and then 2 mg/kg of IV daclizumab monthly for the rest of the 6-month study.
Other Names:
|
| Active Comparator: Intravenous Infliximab Participants randomized to IV infliximab received 3 mg/kg of IV infliximab monthly for 6 months. |
Drug: Intravenous Infliximab
Participants randomized to IV infliximab received 3 mg/kg of IV infliximab monthly for 6 months.
Other Names:
|
| Active Comparator: Oral Rapamycin Participants randomly assigned to rapamycin received 2 mg in capsule form every other day for 6 months. |
Drug: Oral Rapamycin
Participants randomly assigned to rapamycin received 2 mg in capsule form every other day for 6 months.
Other Names:
|
| Other: Observation Participants randomly assigned to the observation group were given injections of either bevacizumab (1.25 mg/0.05 mL or 2.5 mg/0.1 mL) or ranibizumab (0.5 mg) if they presented with recurrence of intraretinal or subretinal fluid as seen on Stratus Optical Coherence Tomography. |
Other: Observation
Participants randomly assigned to the observation group were given injections of either bevacizumab (1.25 mg/0.05 mL or 2.5 mg/0.1 mL) or ranibizumab (0.5 mg) if they presented with recurrence of intraretinal or subretinal fluid as seen on Stratus Optical Coherence Tomography.
|
Outcome Measures
Primary Outcome Measures
- Monthly Rates of Anti-VEGF (Vascular Endothelial Growth Factor) Injections [24 Weeks]
Secondary Outcome Measures
- Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks [Baseline and 6 months (24 weeks) - Baseline and 3.5 months for Patient 7]
The values in the table represent the denominator for the visual acuity in feet. A value of 20 represents "normal" 20/20 vision while increasing values for the denominator represent worsening vision.
- Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks [Baseline and 6 months (24 weeks) - Baseline and 3.5 months for Patient 7]
Eligibility Criteria
Criteria
INCLUSION CRITERIA:
-
Understand and sign the institutional review board (IRB)-approved informed consent document for the study.
-
Age greater than 55 years.
-
In the study eye, diagnosis of AMD defined by the presence of drusen larger than 63 microns.
-
Any anti-angiogenic therapy in the study eye within 7 days of beginning immunosuppressive therapy.
-
In the study eye, the participant's study eye vision is between 20/20 and 20/400.
-
In the study eye, the presence of CNV under the fovea determined by the investigators and defined as any one of the following fluorescein angiographic (FA) features:
-
Early stippled hyperfluorescence of flat retinal pigment epithelium (RPE)and little or mild leakage in the late frames of the fluorescein (occult).
-
Irregular elevation of the RPE that does not exhibit discrete or bright hyperfluorescence in the early transit phase of the angiogram. Stippled hyperfluorescence may be present. Late frames may show persistent fluorescein staining or leakage within a sensory retinal detachment overlying this area (occult).
-
Late-phase leakage of undetermined source with leakage at the level of the RPE in the late-phase frames of the angiogram in which the source of the late leakage cannot be determined from earlier-phase frames of the angiogram (occult).
-
A well-demarcated area of bright hyperfluorescence in the early phase of the angiogram with leakage through the mid- and late-phase frames which obscures the boundaries of the area (classic).
-
For all CNV lesions considered to have occult CNV with no classic CNV, one of the following criteria must be met:
-
A documented loss of visual acuity (5 or more letters of best-corrected visual acuity if both measurements are made using an Early Treatment for Diabetic Retinopathy Study (ETDRS) chart or, a doubling of the visual angle if Snellen acuities are available from either an outside referral center or within the participating center (e.g., 20/80 to 20/160) a doubling of the visual angle is required because of the measurement variability of Snellen acuities).
OR
- Documented FA evidence of a 10% increase in the lesion greatest linear dimension over the 3 months prior to enrollment.
OR
-
Documented blood associated with CNV.
-
The greatest linear dimension of the entire lesion (classic CNV, occult CNV and any features that could obscure the identification of classic or occult CNV) has to be less than or equal to 5400 microns in greatest linear dimension on the retina as measured by the treating ophthalmologist.
-
Retinal photographs and angiography of sufficient quality, allowing assessment of the macular area according to standard clinical practice, can be obtained.
-
Women of childbearing potential must not be pregnant or lactating, must have a negative pregnancy test at screening and must be practicing an adequate method of birth control. Acceptable methods of birth control include intrauterine device (IUD); oral, dermal, implanted or injected contraceptives; tubal ligation; and barrier methods with spermicide.
-
Willingness to comply with the protocol.
EXCLUSION CRITERIA:
-
CNV, in the study eye, associated with other ocular diseases such as pathologic myopia, ocular histoplasmosis or posterior uveitis, etc.
-
Presence of geographic atrophy under the fovea in the study eye.
-
Evidence of retinal angiomatous proliferation as suspected by the presence of intraretinal hemorrhage, intraretinal leakage, adjoining serous pigment epithelial detachment (PED) or the presence of a connecting retinal vessel.
-
The presence of a chorio-retinal anastomosis.
-
Decreased vision, in the study eye, due to retinal disease not attributable to CNV, such as nonexudative forms of AMD, geographic atrophy, inherited retinal dystrophy, uveitis or epiretinal membrane. Participants who have any additional ocular diseases that have irreversibly compromised or, during follow-up, could likely compromise the visual acuity (VA) of the study eye including amblyopia, anterior ischemic optic neuropathy, clinically significant diabetic macular edema, severe non-proliferative diabetic retinopathy, or proliferative diabetic retinopathy.
-
Decreased vision, in the study eye, due to significant media opacity such as corneal disease or cataract, or opacity precluding photography of the retina; a tear (rip) of the RPE; a vitelliform-like lesion of the outer retina (e.g., as in pattern dystrophies or basal laminar drusen), idiopathic parafoveal telangiectasis, or central serous retinopathy.
-
Presence of fibrosis, hemorrhage, pigment epithelial detachments and other hypofluorescent lesions obscuring greater than 50% of the CNV lesion.
-
History of other systemic antiangiogenic treatment or treatment for CNV (not including photodynamic therapy and pegaptanib sodium injections) in the study eye with transpupillary thermotherapy or other local treatment (such as submacular surgery). Previous laser photocoagulation therapy is acceptable, provided it was not subfoveal.
-
Participant with a known underlying systemic disease with evidence of serious or potentially lethal uncontrolled active disease in one or more extraocular organ systems for which a defined effective medical regimen is indicated.
-
Participant with a corneal melting, necrotizing keratitis, or impending vision loss.
-
Participants with history of allergy to/or exposure to mouse protein.
-
Participant with scleritis of infectious etiology.
-
Participant receiving any other investigational therapy or another anti-tumor necrosis factor (TNF) agent that would interfere with the ability to evaluate the safety or efficacy of infliximab.
-
Participant has significant active infection requiring hospitalization.
-
Participant with multiple sclerosis.
-
Participant has severe (class 3/4) congestive heart failure.
-
Participant has a history of cancer within the past 5 years other than basal or squamous cell carcinoma.
-
Participant is pregnant or lactating.
-
Participant with posterior scleritis.
-
Participant has evidence of liver disease (any etiology). History of moderate to severe abnormal liver function, unless documented evidence of normal liver enzymes is provided.
-
Participant has positive PPD (tuberculosis test) unless cleared by Internal Medicine.
-
Participant has positive Chest X-ray showing acute pulmonary disease.
-
Participant has unexplained hematuria.
-
Participant has a history of alkylating therapy use.
-
Current exam evidence of ocular toxoplasmosis; pseudoexfoliation; external ocular infection, including conjunctivitis; chalazion; significant blepharitis; or aphakia in the study eye (pseudophakic participants are eligible).
-
Intraocular surgery (including lens replacement surgery) within 6 weeks prior to randomization.
-
Recent history of (within the last 6 months), or current acute ocular or periocular infection (including any history of ocular herpes zoster or simplex).
-
Known hypersensitivity/allergy to verteporfin, porfimer sodium, or other porphyrins, porphyria or other porphyrin sensitivity, or hypersensitivity to sunlight or bright artificial light. Participation in any other clinical study or are receiving, or have received any experimental systemic treatment for AMD (e.g., retinoic acid, thalidomide). Local therapy for AMD is permitted.
-
Medical problems that make consistent follow-up over the treatment period unlikely (e.g., stroke, severe myocardial infarction (MI), end stage malignancy), any contraindications to performing the necessary diagnostic studies (i.e., known allergy to fluorescein dyes etc.), or in general a poor medical risk because of other systemic diseases or active uncontrolled infections.
-
Participant has a history of moderate to severe abnormal liver function, unless documented evidence of normal liver enzymes is provided.
-
Participant has a history of active pulmonary tuberculosis.
-
Participant has a history of active viral hepatitis.
-
Participant has chronic continued Ketoconazole use.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland | United States | 20892 |
Sponsors and Collaborators
- National Eye Institute (NEI)
Investigators
- Principal Investigator: Robert Nussenblatt, MD, MPH, National Eye Institute (NEI)
Study Documents (Full-Text)
None provided.More Information
Publications
- Aeberli D, Oertle S, Mauron H, Reichenbach S, Jordi B, Villiger PM. Inhibition of the TNF-pathway: use of infliximab and etanercept as remission-inducing agents in cases of therapy-resistant chronic inflammatory disorders. Swiss Med Wkly. 2002 Jul 27;132(29-30):414-22.
- Antoni C, Dechant C, Hanns-Martin Lorenz PD, Wendler J, Ogilvie A, Lueftl M, Kalden-Nemeth D, Kalden JR, Manger B. Open-label study of infliximab treatment for psoriatic arthritis: clinical and magnetic resonance imaging measurements of reduction of inflammation. Arthritis Rheum. 2002 Oct 15;47(5):506-12.
- Bian ZM, Elner SG, Strieter RM, Kunkel SL, Lukacs NW, Elner VM. IL-4 potentiates IL-1beta- and TNF-alpha-stimulated IL-8 and MCP-1 protein production in human retinal pigment epithelial cells. Curr Eye Res. 1999 May;18(5):349-57.
- 060111
- 06-EI-0111
Study Results
Participant Flow
| Recruitment Details | The study was conducted at the Clinical Center, NIH. A total of 13 participants met the eligibility criteria for the study and were enrolled from September 2006 to May 2008. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Intravenous Daclizumab | Intravenous Infliximab | Oral Rapamycin | Observation |
|---|---|---|---|---|
| Arm/Group Description | Participants randomly assigned to intravenous (IV) daclizumab received 8 mg/kg of IV daclizumab at baseline, then 4 mg/kg of IV daclizumab at Week 2 and then 2 mg/kg of IV daclizumab monthly for the rest of the 6-month study. | Participants randomized to IV infliximab received 3 mg/kg of IV infliximab monthly for 6 months. | Participants randomly assigned to rapamycin received 2 mg in capsule form every other day for 6 months. | Participants randomly assigned to the observation group were given injections of either bevacizumab (1.25 mg/0.05 mL or 2.5 mg/0.1 mL) or ranibizumab (0.5 mg) if they presented with recurrence of intraretinal or subretinal fluid as seen on Stratus Optical Coherence Tomography. |
| Period Title: Overall Study | ||||
| STARTED | 4 | 3 | 3 | 3 |
| COMPLETED | 3 | 3 | 2 | 3 |
| NOT COMPLETED | 1 | 0 | 1 | 0 |
Baseline Characteristics
| Arm/Group Title | Intravenous Daclizumab | Intravenous Infliximab | Oral Rapamycin | Observation | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Participants randomly assigned to intravenous (IV) daclizumab received 8 mg/kg of IV daclizumab at baseline, then 4 mg/kg of IV daclizumab at Week 2 and then 2 mg/kg of IV daclizumab monthly for the rest of the 6-month study. | Participants randomized to IV infliximab received 3 mg/kg of IV infliximab monthly for 6 months. | Participants randomly assigned to rapamycin received 2 mg in capsule form every other day for 6 months. | Participants randomly assigned to the observation group were given injections of either bevacizumab (1.25 mg/0.05 mL or 2.5 mg/0.1 mL) or ranibizumab (0.5 mg) if they presented with recurrence of intraretinal or subretinal fluid as seen on Stratus Optical Coherence Tomography. | Total of all reporting groups |
| Overall Participants | 4 | 3 | 3 | 3 | 13 |
| Age (Count of Participants) | |||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
1
25%
|
0
0%
|
0
0%
|
0
0%
|
1
7.7%
|
| >=65 years |
3
75%
|
3
100%
|
3
100%
|
3
100%
|
12
92.3%
|
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
79
(13)
|
77
(8)
|
78
(7)
|
87
(4)
|
80
(9)
|
| Gender (Count of Participants) | |||||
| Female |
4
100%
|
2
66.7%
|
3
100%
|
3
100%
|
12
92.3%
|
| Male |
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
1
7.7%
|
| Region of Enrollment (participants) [Number] | |||||
| United States |
4
100%
|
3
100%
|
3
100%
|
3
100%
|
13
100%
|
Outcome Measures
| Title | Monthly Rates of Anti-VEGF (Vascular Endothelial Growth Factor) Injections |
|---|---|
| Description | |
| Time Frame | 24 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Intravenous Daclizumab | Intravenous Infliximab | Oral Rapamycin | Observation |
|---|---|---|---|---|
| Arm/Group Description | Participants randomly assigned to intravenous (IV) daclizumab received 8 mg/kg of IV daclizumab at baseline, then 4 mg/kg of IV daclizumab at Week 2 and then 2 mg/kg of IV daclizumab monthly for the rest of the 6-month study. | Participants randomized to IV infliximab received 3 mg/kg of IV infliximab monthly for 6 months. | Participants randomly assigned to rapamycin received 2 mg in capsule form every other day for 6 months. | Participants randomly assigned to the observation group were given injections of either bevacizumab (1.25 mg/0.05 mL or 2.5 mg/0.1 mL) or ranibizumab (0.5 mg) if they presented with recurrence of intraretinal or subretinal fluid as seen on Stratus Optical Coherence Tomography. |
| Measure Participants | 4 | 3 | 3 | 3 |
| Median (Full Range) [Injections per Month] |
0.42
|
0.83
|
0.34
|
0.83
|
| Title | Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks |
|---|---|
| Description | The values in the table represent the denominator for the visual acuity in feet. A value of 20 represents "normal" 20/20 vision while increasing values for the denominator represent worsening vision. |
| Time Frame | Baseline and 6 months (24 weeks) - Baseline and 3.5 months for Patient 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Baseline Vision - Study Eye | Sixth-Month Vision - Study Eye | Baseline Vision - Fellow Eye | Sixth-Month Vision - Fellow Eye |
|---|---|---|---|---|
| Arm/Group Description | ||||
| Measure Participants | 13 | 13 | 13 | 13 |
| Rapamycin Patient 1 |
40
|
25
|
400
|
640
|
| Rapamycin Patient 7 (Baseline and 3.5 months) |
63
|
50
|
640
|
640
|
| Rapamycin Patient 12t |
32
|
32
|
32
|
32
|
| Daclizumab Patient 3 |
40
|
40
|
40
|
32
|
| Daclizumab Patient 8 |
32
|
32
|
32
|
32
|
| Daclizumab Patient 9 |
250
|
250
|
63
|
40
|
| Daclizumab Patient 13 |
50
|
40
|
25
|
20
|
| Infliximab Patient 2 |
40
|
32
|
63
|
125
|
| Infliximab Patient 6 |
250
|
800
|
63
|
80
|
| Infliximab Patient 10 |
50
|
32
|
125
|
125
|
| Observation Patient 4 |
63
|
63
|
40
|
25
|
| Observation Patient 5 |
50
|
25
|
NA
|
NA
|
| Observation Patient 11 |
32
|
50
|
200
|
63
|
| Title | Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks |
|---|---|
| Description | |
| Time Frame | Baseline and 6 months (24 weeks) - Baseline and 3.5 months for Patient 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Baseline OCT - Study Eye | Sixth-Month OCT - Study Eye | Baseline OCT - Fellow Eye | Sixth-Month OCT - Fellow Eye |
|---|---|---|---|---|
| Arm/Group Description | ||||
| Measure Participants | 13 | 13 | 13 | 13 |
| Rapamycin Patient 1 |
234
|
230
|
211
|
203
|
| Rapamycin Patient 7 (Baseline and 3.5 months) |
361
|
239
|
242
|
186
|
| Rapamycin Patient 12t |
327
|
264
|
226
|
205
|
| Daclizumab Patient 3 |
216
|
189
|
352
|
206
|
| Daclizumab Patient 8 |
185
|
208
|
218
|
149
|
| Daclizumab Patient 9 |
297
|
196
|
215
|
210
|
| Daclizumab Patient 13 |
329
|
344
|
305
|
317
|
| Infliximab Patient 2 |
205
|
177
|
190
|
181
|
| Infliximab Patient 6 |
290
|
243
|
262
|
252
|
| Infliximab Patient 10 |
291
|
288
|
453
|
347
|
| Observation Patient 4 |
229
|
196
|
189
|
171
|
| Observation Patient 5 |
426
|
225
|
270
|
213
|
| Observation Patient 11 |
318
|
305
|
158
|
169
|
Adverse Events
| Time Frame | February 14, 2006 through December 30, 2009 | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Intravenous Daclizumab | Intravenous Infliximab | Oral Rapamycin | Observation | ||||
| Arm/Group Description | Participants randomly assigned to intravenous (IV) daclizumab received 8 mg/kg of IV daclizumab at baseline, then 4 mg/kg of IV daclizumab at Week 2 and then 2 mg/kg of IV daclizumab monthly for the rest of the 6-month study. | Participants randomized to IV infliximab received 3 mg/kg of IV infliximab monthly for 6 months. | Participants randomly assigned to rapamycin received 2 mg in capsule form every other day for 6 months. | Participants randomly assigned to the observation group were given injections of either bevacizumab (1.25 mg/0.05 mL or 2.5 mg/0.1 mL) or ranibizumab (0.5 mg) if they presented with recurrence of intraretinal or subretinal fluid as seen on Stratus Optical Coherence Tomography. | ||||
All Cause Mortality |
||||||||
| Intravenous Daclizumab | Intravenous Infliximab | Oral Rapamycin | Observation | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Intravenous Daclizumab | Intravenous Infliximab | Oral Rapamycin | Observation | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | ||||
| Nervous system disorders | ||||||||
| Episode of right sided numbness | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||
| Intravenous Daclizumab | Intravenous Infliximab | Oral Rapamycin | Observation | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/4 (100%) | 3/3 (100%) | 3/3 (100%) | 3/3 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Decreased Albumin | 4/4 (100%) | 5 | 2/3 (66.7%) | 2 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 |
| Elevated Blood Urea Nitrogen | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Elevated C02 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 2 | 0/3 (0%) | 0 |
| Decreased Phosphorus | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Elevated Phosphorus | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Elevated Chloride | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 |
| Elevated Red Blood Cell Count | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 2/3 (66.7%) | 2 | 2/3 (66.7%) | 2 |
| Ankle Edema | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Elevated Ethrocyte Sedimentation Rate | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Elevated Low-density Lipoprotein | 2/4 (50%) | 2 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Elevated Cholesterol | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 |
| Decreased Hematocrit | 0/4 (0%) | 0 | 2/3 (66.7%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Elevated Basophils | 3/4 (75%) | 3 | 2/3 (66.7%) | 2 | 0/3 (0%) | 0 | 2/3 (66.7%) | 2 |
| Elevated Bilirubin | 1/4 (25%) | 1 | 2/3 (66.7%) | 2 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 |
| Elevated Eosinophils | 0/4 (0%) | 0 | 2/3 (66.7%) | 2 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 |
| Decreased Red Cell Distribution Width | 2/4 (50%) | 2 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 |
| Elevated Uric Acid | 2/4 (50%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 |
| Elevated Lymphocytes | 1/4 (25%) | 1 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 2 |
| Decreased Sodium | 2/4 (50%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Elevated White Blood Cell Count | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Elevated Neutrophils | 1/4 (25%) | 1 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Elevated Potassium | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 |
| Elevated Alanine Transaminase | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 |
| Elevated Aspartate Aminotransferase | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 |
| Elevated Hematocrit | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 2 |
| Elevated Hemoglobin | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 |
| Elevated Thyroid Stimulating Hormone | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Elevated Monocytes | 3/4 (75%) | 3 | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 2 | 0/3 (0%) | 0 |
| Hypercholesteremia | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Elevated Magnesium | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 |
| Elevated Lactate Dehydrogenase | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Decreased Chloride | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Decreased Hemoglobin | 1/4 (25%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Decreased Magnesium | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Decreased Low-density Lipoprotein | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Decreased Red Blood Cell Count | 1/4 (25%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Elevated Glucose | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Decreased Neutrophils | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 |
| Decreased Uric Acid | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Decreased Creatinine Kinase | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Decreased Eosinophils | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Decreased Alkaline Phosphatase | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Decreased Neutrophils | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Cardiac disorders | ||||||||
| Aortic Anneurysm | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Fluttering in Chest | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Irregular Heart Rate | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Hypertension | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 |
| Ear and labyrinth disorders | ||||||||
| Tinnitus | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Eye disorders | ||||||||
| Blurred Vision | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Lacrimal Gland Lesion | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Pigmented Papule on Eyelid | 1/4 (25%) | 1 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 |
| Seborrheic Keratoses Eyelid | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Iris Nevi | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Vitreous Syneresis | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Ptosis | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 |
| Vitreous Detachment | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 |
| Vision Decrease | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Metamorphosia | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Fecal Incontinence | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Nausea | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Colitis | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Discomfort Defacating | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| General disorders | ||||||||
| Weakness | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Achiness | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Laryngitis | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Runny Nose | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Elevated Lipids | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Headache | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Infections and infestations | ||||||||
| Urinary Tract Infection | 1/4 (25%) | 1 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Scratchy Throat | 1/4 (25%) | 1 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Flu | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Foot Ulcer | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Diarrhea | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Ear Infection | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Upper Respiratory Infection | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Conjunctivitis | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| Fall | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 2 | 0/3 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| Electrolyte Imbalance | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthritis Hands | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Leg Cramps | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Shoulder Pain | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Polymialgia Rheumatica | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Nervous system disorders | ||||||||
| Tingling Hands | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Migraine Symptoms | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Sciatica | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Renal and urinary disorders | ||||||||
| Stress Incontinence | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Elevated White Blood Cells in Urine | 2/4 (50%) | 2 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Elevated Red Blood Cells in Urine | 1/4 (25%) | 1 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 |
| Leukocyte Esterase in Urine | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Bronchitis | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Cough | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||
| Pruritus on Torso and Upper Arms | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Rash | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Robert Nussenblatt, MD, MPH |
|---|---|
| Organization | NEI |
| Phone | 301-496-3123 |
| robert.nussenblatt@nih.gov |
- 060111
- 06-EI-0111