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Alzheimer's DiseasePhase 1NCT01716637

Short Term Efficacy and Safety of Perispinal Administration of Etanercept in Mild to Moderate Alzheimer's Disease

A Phase 1 study testing Etanercept and Curcum.Luteol.Theaflav.Lip.Acid,FishOil,Quercet.,Resveratr. in people with Alzheimer's Disease, run by Life Extension Foundation Inc. at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 60 to 85 years
Conditions the study is for
Alzheimer's Disease
What is being tested?
Etanercept and Curcum.Luteol.Theaflav.Lip.Acid,FishOil,Quercet.,Resveratr.
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
2 sitesUnited States
Study dates
Feb 2010to May 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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
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  • 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.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Paul H. Wand M.D., P.A.

    Coral Springs, Florida, 33065

  • Brain Matters Research

    Delray Beach, Florida, 33445

Other trials in United States

About this study

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.

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.

Read more

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.

Being tested
Etanercept, Curcum.Luteol.Theaflav.Lip.Acid,FishOil,Quercet.,Resveratr.
Keywords
Alzheimer's Disease, Dementia, Cognitive decline, Cognitive disorder, Degenerative brain disease, Cognitive impairment, Memory loss, TNF-alpha
Medical subject headings
Alzheimer Disease, Dementia, Cognitive Dysfunction, Memory Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EtanerceptBiological

    Also called Enbrel®

  • Curcum.Luteol.Theaflav.Lip.Acid,FishOil,Quercet.,Resveratr.Dietary supplement

    Also called Super Bio-Curcumin, Super Omega-3, Optimized Quercetin, Optimized Resveratrol

Study groups in NCT01716637
Study groupRoleWhat they receive
EtanerceptActive comparator25 mg administered weekly for 6 weeks
Receives: Biological: Etanercept; Dietary Supplement: Curcum.Luteol.Theaflav.Lip.Acid,FishOil,Quercet.,Resveratr.
Nutritional SupplementsActive comparatorNutritional supplements administered daily for 6 weeks in each period as well as an additional 12 weeks following visit 15.
Receives: Dietary Supplement: Curcum.Luteol.Theaflav.Lip.Acid,FishOil,Quercet.,Resveratr.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Difference in effects of treatment for 6 weeks with etanercept + nutritional supplements versus nutritional supplements alone on the Mini-Mental Status Examination (MMSE) score.

    Measured: 16 weeks

Secondary outcomes (2)

  1. 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.

    Measured: 16 weeks

  2. Difference in the effects of treatment for 6 weeks with etanercept + nutritional supplements versus nutritional supplements alone on the Montreal Cognitive Assessment (MoCA) score.

    Measured: 16 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Oct 2012 (estimated)
  2. Study startFeb 2010
  3. Primary completionOct 2015
  4. Study completionMay 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Health services research
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
12 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01716637
Sponsor's protocol ID
CL025
Status last verified
May 2016
First submitted
5 Oct 2012
Last updated
12 May 2016
Results posted
No
Data monitoring committee
No

Publications

  • Centers for Disease Control and Prevention website. CDC Features: Alzheimer's Disease. http://www.cdc.gov/Features/Alzheimers/. 12-15-2008. 6-23-2009.

  • 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.

    PubMed 11754997

  • Alzheimer's Disease Education & Referral (ADEAR) Center, National Institutes of Health. Alzheimer's Disease Fact Sheet. 2008.

  • 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.

    PubMed 15639313

  • Tarkowski E, Andreasen N, Tarkowski A, Blennow K. Intrathecal inflammation precedes development of Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2003 Sep;74(9):1200-5. doi: 10.1136/jnnp.74.9.1200.

    PubMed 12933918

  • McGeer PL, McGeer EG. Local neuroinflammation and the progression of Alzheimer's disease. J Neurovirol. 2002 Dec;8(6):529-38. doi: 10.1080/13550280290100969.

    PubMed 12476347

  • Kaur C, Ling EA. Antioxidants and neuroprotection in the adult and developing central nervous system. Curr Med Chem. 2008;15(29):3068-80. doi: 10.2174/092986708786848640.

    PubMed 19075654

  • Tobinick E, Gross H, Weinberger A, Cohen H. TNF-alpha modulation for treatment of Alzheimer's disease: a 6-month pilot study. MedGenMed. 2006 Apr 26;8(2):25.

    PubMed 16926764

  • Tarkowski E, Liljeroth AM, Minthon L, Tarkowski A, Wallin A, Blennow K. Cerebral pattern of pro- and anti-inflammatory cytokines in dementias. Brain Res Bull. 2003 Aug 15;61(3):255-60. doi: 10.1016/s0361-9230(03)00088-1.

    PubMed 12909295

  • Laws SM, Perneczky R, Wagenpfeil S, Muller U, Forstl H, Martins RN, Kurz A, Riemenschneider M. TNF polymorphisms in Alzheimer disease and functional implications on CSF beta-amyloid levels. Hum Mutat. 2005 Jul;26(1):29-35. doi: 10.1002/humu.20180.

    PubMed 15895461

  • Tobinick EL, Gross H. Rapid improvement in verbal fluency and aphasia following perispinal etanercept in Alzheimer's disease. BMC Neurol. 2008 Jul 21;8:27. doi: 10.1186/1471-2377-8-27.

    PubMed 18644112

  • Becker RE. Modifying clinical trial designs to test treatments for clinical significance in individual patients. Clin Drug Invest 2001:21:727-733.

  • Griffin WS. Perispinal etanercept: potential as an Alzheimer therapeutic. J Neuroinflammation. 2008 Jan 10;5:3. doi: 10.1186/1742-2094-5-3.

    PubMed 18186919

  • Tobinick E. Perispinal etanercept for neuroinflammatory disorders. Drug Discov Today. 2009 Feb;14(3-4):168-77. doi: 10.1016/j.drudis.2008.10.005. Epub 2008 Dec 6.

    PubMed 19027875

  • Tobinick E. Perispinal etanercept for treatment of Alzheimer's disease. Curr Alzheimer Res. 2007 Dec;4(5):550-2. doi: 10.2174/156720507783018217.

    PubMed 18220520

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Etanercept and Curcum.Luteol.Theaflav.Lip.Acid,FishOil,Quercet.,Resveratr. in people with Alzheimer's Disease, run by Life Extension Foundation Inc. at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 May 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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. (time frame: 16 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01716637, which also lists 37 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2016.

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