Clinical trial NCT01716637: Short Term Efficacy and Safety of Perispinal Administration of Etanercept in Mild to Moderate Alzheimer's Disease
Official title: Open Label,Crossover,Pilot Study to Assess the Efficacy & Safety of Perispinal Admin.of Etanercept(Enbrel®) in Comb.w/Nutritional Supplements vs. Nutritional Supplements Alone in Subj. w/Mild to Mod. Alzheimer's Disease Receiving Std. Care.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer's Disease
Keywords: Alzheimer's Disease
Dementia
Cognitive decline
Cognitive disorder
Degenerative brain disease
Cognitive impairment
Memory loss
TNF-alpha
Lead sponsor: Life Extension Foundation Inc.
Sponsor class: OTHER
First posted: 2012-10-30
Enrollment: 12
Sex: ALL
Minimum age (years): 60
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Subject is aged 60-85 years
* Subject has a diagnosis of Alzheimer's disease according to the NINCDS- ADRDA criteria (National Institute of Neurological and Communicative Disorders and Stroke NINCDS\] and Alzheimer's Disease and Related Disorders Association \[ADRDA\]).
* Subject is not institutionalized (for example, lives independently, lives independently in a residential home for the elderly, or is a day patient at a care center)
* Subject has a Hachinski Ischemia Score of ≤ 4.
* Subject has a total MoCA score of \< 26 at screening.
* Subject has an MMSE score of 11 to 24 at screening.
* Subject has an ADAS-cog score of 12 to 25 at screening.
* Subject has experienced a gradual and progressive cognitive decline in the 6 months before the screening visit.
* Subject provides informed consent to participate in the study or has a legally acceptable representative who provides consent.
* Subject has a responsible caregiver who consents to supporting the subject in his/her study participation (for example, by accompanying the subject on each study visit).
* Subject is surgically sterile, agrees to use an acceptable method of birth control as defined in section 5.4 or, for females, is post- menopausal.
* Subject agrees to stop taking any vitamin, mineral, or dietary supplements he/she is currently taking that have any components of the nutritional supplements utilized in the study at least 7 days before randomization (Visit 2) and agrees to not use any new vitamin, mineral, or dietary supplement product other than those provided by the investigator until after the subject is discharged from the study.

Exclusion Criteria:

* A neurologic disorder, such as seizures, multiple sclerosis, neurodegenerative disorders (eg, Parkinson's disease), or dementia other than Alzheimer's type (including that caused by small strokes or cerebrovascular disease)
* Cognitive impairment from any condition other than Alzheimer's disease, such as that resulting from acute cerebral trauma, cerebral damage due to a lack of oxygen, infections such as meningitis or AIDS, significant endocrine or metabolic disease, mental retardation, or a brain tumor
* Cardiovascular or cerebrovascular disease, such as congestive heart failure, uncontrolled hypertension (BP ≥ 140/90 mmHg at screening), and a history of stroke
* Renal impairment/disease, defined as serum creatinine \> 1.5 mg/dL
* Hepatic impairment, defined as Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) \> 3 times the upper limit of normal OR has a history of a positive blood screen for hepatitis B surface antigen or hepatitis C antibody.
* Type I or II diabetes mellitus
* Significant or uncontrolled psychiatric disease
* Gastrointestinal disease, such as active peptic ulcer, gallstones, gallbladder disease, or biliary tract obstruction, or a history of cholecystectomy
* Hematologic disorders
* Pulmonary or lung disorders
* Immune system disorder, such as HIV/AIDS
* History of cancer within 10 years before screening (except localized skin cancer without metastases or in situ cervical cancer)
* History of chronic or recurrent infection (including tuberculosis) OR, in the 7 days before Visit 2 (randomization), any known infection or body temperature \> 38.6º C (101.5º F)
* Subject is pregnant or breastfeeding at screening.
* Subject has intolerance or allergy to Enbrel®, latex, or any of Enbrel's components.
* Subject is currently consuming more than 6 standard alcoholic beverages a week. A standard alcoholic beverage is defined as 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of liquor.
* Subject is currently taking and unable or unwilling to stop taking anticoagulant or antiplatelet herbs and supplements such as angelica, clove, danshen, garlic, ginger, ginkgo, Panax ginseng, red clover, or willow for at least 7 days before the randomization visit (Visit 2) and throughout the study.
* Subject is currently taking and unable or unwilling to stop taking any of the prohibited medications in protocol section 5.3.2 for at least 7 days before the randomization visit (Visit 2) and throughout the study.
* Subject had major surgery within the 4 weeks before screening.
* Subject has any condition or abnormality that, in the opinion of the investigator, would compromise the safety of the subject or the quality of the study data.
* Subject is participating or has participated in another research study within 30 days before the screening visit
* Subject or subject's caregiver is unable or unwilling to comply with the study procedures.

Primary outcomes:
measure: Difference in effects of treatment for 6 weeks with etanercept + nutritional supplements versus nutritional supplements alone on the Mini-Mental Status Examination (MMSE) score.
timeFrame: 16 weeks
Secondary outcomes:
measure: 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.
timeFrame: 16 weeks
measure: Difference in the effects of treatment for 6 weeks with etanercept + nutritional supplements versus nutritional supplements alone on the Montreal Cognitive Assessment (MoCA) score.
timeFrame: 16 weeks
Other outcomes:
measure: 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.
timeFrame: 28 weeks
measure: Difference in short term effects of etanercept on the MMSE score before and two hours after perispinal administration of etanercept.
timeFrame: 16 weeks
measure: 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.
timeFrame: 16 weeks
measure: 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.
timeFrame: 28 weeks
measure: 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.
timeFrame: 28 weeks
measure: Difference in short term effects of etanercept on the ADAS-cog score before and two hours after perispinal administration of etanercept.
timeFrame: 16 weeks
measure: Difference in short term effects of etanercept on the MoCA score before and two hours after perispinal administration of etanercept.
timeFrame: 16 weeks
measure: 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.
timeFrame: 16 weeks
Locations:
city: Coral Springs
country: United States
facility: Paul H. Wand M.D., P.A.
state: Florida
city: Delray Beach
country: United States
facility: Brain Matters Research
state: Florida
Study officials:
affiliation: Paul H. Wand M.D., P.A.
name: Paul H. Wand, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Brain Matters Research Inc.
name: Mark L. Brody, M.D.
role: PRINCIPAL_INVESTIGATOR
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