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While the cause of AD is still unknown, evidence suggests it develops because of a complex series of events in the brain that occur over time. Two pathways possibly involved in development of AD are inflammation and oxidative stress. Scientists have linked chronic inflammatory events in the brain with the onset and progression of Alzheimer's Disease. Oxidative stress has also been implicated in the pathogenesis of a number of neurological disorders including Alzheimer's Disease.
Etanercept (Enbrel®) is an approved drug for the treatment of several forms of arthritis when administered by injection. Some research suggests that etanercept, when administered by injection into the tissues close to the spinal column (perispinally), may modulate certain aspects of the immune system and provide some beneficial effect for people with Alzheimer's disease. Studies suggest that supplementation with specific nutrients may also have a positive effect in support of cognitive function.
This study will be conducted at one research office with volunteers who have been diagnosed with mild to moderate Alzheimer's disease. Each qualifying participant will be randomly assigned to receive an etanercept injection plus nutritional supplements for 6 weeks followed by a crossover and a washout period of 4 weeks to then receiving nutritional supplements alone or vice versa for another 6 weeks.
Participants will undergo blood and urine safety assessments at the beginning and end of each 6 week treatment period. During 4 of the 6 weekly visits in the treatment period with the injections, you will complete the cognitive tests twice; once before and once 2 hours after the injection. During 4 of the 6 weekly visits in the treatment period without the injections, you will also complete the cognitive tests twice; once before and once 2 hours after being asked to lie down onto a table for 5 minutes. You will be allowed to continue your standard of care for Alzheimer's disease throughout your participation in the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Etanercept | Active Comparator | 25 mg administered weekly for 6 weeks |
|
| Nutritional Supplements | Active Comparator | Nutritional supplements administered daily for 6 weeks in each period as well as an additional 12 weeks following visit 15. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Etanercept | Biological |
|
| |
| Curcum.Luteol.Theaflav.Lip.Acid,FishOil,Quercet.,Resveratr. |
| Measure | Description | Time Frame |
|---|---|---|
| Difference in effects of treatment for 6 weeks with etanercept + nutritional supplements versus nutritional supplements alone on the Mini-Mental Status Examination (MMSE) score. | 16 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Difference in the effects of treatment for 6 weeks with etanercept + nutritional supplements versus nutritional supplements alone on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) score. | 16 weeks | |
| Difference in the effects of treatment for 6 weeks with etanercept + nutritional supplements versus nutritional supplements alone on the Montreal Cognitive Assessment (MoCA) score. |
| Measure | Description | Time Frame |
|---|---|---|
| Difference in the effects of treatment for 6 weeks as well as an additional 12 weeks following visit 15 with nutritional supplementation alone on the MMSE score. | 28 weeks | |
| Difference in short term effects of etanercept on the MMSE score before and two hours after perispinal administration of etanercept. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Paul H. Wand, M.D. | Paul H. Wand M.D., P.A. | Principal Investigator |
| Mark L. Brody, M.D. | Brain Matters Research Inc. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Paul H. Wand M.D., P.A. | Coral Springs | Florida | 33065 | United States | ||
| Brain Matters Research |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Background | Centers for Disease Control and Prevention website. CDC Features: Alzheimer's Disease. http://www.cdc.gov/Features/Alzheimers/. 12-15-2008. 6-23-2009. | ||
| 11754997 | Background | Mrak RE, Griffin WS. Interleukin-1, neuroinflammation, and Alzheimer's disease. Neurobiol Aging. 2001 Nov-Dec;22(6):903-8. doi: 10.1016/s0197-4580(01)00287-1. | |
| Background | Alzheimer's Disease Education & Referral (ADEAR) Center, National Institutes of Health. Alzheimer's Disease Fact Sheet. 2008. | ||
| 15639313 |
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| Dietary Supplement |
|
|
| 16 weeks |
| 16 weeks |
| To determine the safety and tolerability of nutritional supplements with perispinal adminstration of etanercept, as measured by various laboratory markers, vital signs (blood pressure and heart rate), and adverse events. | 16 weeks |
| Difference in the effects of treatment for 6 weeks as well as an additional 12 weeks following visit 15 with nutritional supplementation alone on the ADAS-cog score. | 28 weeks |
| Difference in the effects of treatment for 6 weeks as well as an additional 12 weeks following visit 15 with nutritional supplementation alone on the MoCA score. | 28 weeks |
| Difference in short term effects of etanercept on the ADAS-cog score before and two hours after perispinal administration of etanercept. | 16 weeks |
| Difference in short term effects of etanercept on the MoCA score before and two hours after perispinal administration of etanercept. | 16 weeks |
| To determine the safety and tolerability of nutritional supplements without perispinal adminstration of etanercept, as measured by various laboratory markers, vital signs (blood pressure and heart rate), and adverse events. | 16 weeks |
| Delray Beach |
| Florida |
| 33445 |
| United States |
| Background |
| Mrak RE, Griffin WS. Glia and their cytokines in progression of neurodegeneration. Neurobiol Aging. 2005 Mar;26(3):349-54. doi: 10.1016/j.neurobiolaging.2004.05.010. |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| D003704 | Dementia |
| D060825 | Cognitive Dysfunction |
| D008569 | Memory Disorders |
| ID | Term |
|---|---|
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D003072 | Cognition Disorders |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000068800 | Etanercept |
| ID | Term |
|---|---|
| D007141 | Immunoglobulin Fc Fragments |
| D007128 | Immunoglobulin Fragments |
| D010446 | Peptide Fragments |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D007127 | Immunoglobulin Constant Regions |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D018124 | Receptors, Tumor Necrosis Factor |
| D018121 | Receptors, Cytokine |
| D011971 | Receptors, Immunologic |
| D011956 | Receptors, Cell Surface |
| D008565 | Membrane Proteins |
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