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Trial registered on ANZCTR


Registration number
ACTRN12612000876897
Ethics application status
Approved
Date submitted
16/08/2012
Date registered
17/08/2012
Date last updated
9/09/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of Etanercept in Australian patients with Progressive Dementia
Scientific title
Phase I Clinical trial of the safe use of perispinal Etanercept (Tumour Necrosis Factor-Alpha blocker) in Australian patients with progressive dementia
Secondary ID [1] 280951 0
Nil
Universal Trial Number (UTN)
U1111-1133-1715
Trial acronym
Nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dementia 287048 0
Condition category
Condition code
Mental Health 287376 287376 0 0
Other mental health disorders
Neurological 287377 287377 0 0
Dementias
Inflammatory and Immune System 287378 287378 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Etanercept (Enbrel) 25mg or less prepared in 1ml syringe as 25mg/1ml, injected subcutaneously at the back of the neck in an area that drains into the blood supply that goes towards the brain spaces. The treatment consists of a weekly injection of Etanercept over a period of 4 weeks by a trained and certified medical practitioner, followed by a follow-up assessment on the 5th week. Participant will be tilted forward on a purpose built tilt bed after the injection lowering the head for 5 minutes to aid the Etanercept enter the brain spaces.
Intervention code [1] 285385 0
Treatment: Drugs
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 287649 0
Safe use by observation, recording and reporting on side effects including frequency of adverse events and serious adverse events. Common side effects the participant may or may not experience include injection site reaction, upper respiratory infections (including sinus infection), and headaches.

Clinical assessment by physical examination including skin, eyes, ears, throat, cardiac, respiratory, gastrointestinal, genitourinary, musculoskeletal and nervous systems.
Timepoint [1] 287649 0
Post-intervention observation over a 2-hour period.
Primary outcome [2] 287650 0
Measure of Cognitive effects using Alzheimer's Disease Assessment Scale - Cognitive section (ADAS-cog), Addenbrooke's Cognitive Examination (ACE-R) which includes an embedded Mini-Mental State Examination (MMSE), Severe Impairment Battery (SIB) and Activities of Daily Living (ADL-19)
Timepoint [2] 287650 0
a) Pre-intervention (Baseline)
b) Post-intervention (weekly)
c) Follow-up (at the end of 4 weeks treatment)
Secondary outcome [1] 298583 0
Measure of serum change in inflammatory biomarkers by blood sample profile.
Timepoint [1] 298583 0
a) Pre-invention (Baseline)
b) Post-invention (weekly)
c) Follow-up (at the end of 4 weeks treatment)
Secondary outcome [2] 298794 0
Clinical assessment of vital signs: seated blood pressure and heart rate measured by standard blood pressure monitor, respiration by observation of signs of breathing difficulties, temperature by infrared thermometer and weight.
Timepoint [2] 298794 0
a) Pre-invention (Baseline)
b) Post-invention (weekly)
c) Follow-up (at the end of 4 weeks treatment)

Eligibility
Key inclusion criteria
1) informed consent (i.e., authority received from participant themselves and/or an approved Surrogate Decision Maker/Guardian according to the appropriate Guardianship and Administration Tribunal (GAAT) in QLD or NSW.
2) Fulfil Diagnostic & Statistical Manual (DSM-IV-TR) criteria for diagnosis of dementia of the Alzheimer type
3) Have a diagnosis of probable Alzheimer's Disease meeting National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable Alzheimer's disease.
4) CT/MRI brain scans or initial SPECT exam compatible with diagnosis of AD.
5) Age of onset of AD at 70 years of age or close to this.
6) MMSE 10-20, and prescribed Donepezil, dose should be stable for at least 3 months before the trial, and should be unchanged during the trial
Minimum age
70 Years
Maximum age
88 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Parkinson's Disease, Dementia with Lewy Bodies or clinically significant Parkinsonian symptoms.
2) Hallucinations, delirium –associated with Lewy Bodies.
3) Diagnosis of Aphasia and/or Bizarre behaviour (such as violence) – often attributes of SD or FTD.
4) Rapidly declining patients - AD progression is slow. Rapid decline indicates another factor is involved.
5) Patients who show ENBREL contraindications:
- History of active or chronic infection
- Lymphoma, active or in the past Cancer
- Multiple Sclerosis
- Demyelinating disease
- Uncontrolled diabetes mellitus
- Patients prescribed Kineret (Anakinra) or Abatacept)
6) Patients who have or are:
- Hematologic disease
- Congestive Heart Failure
- Immunosuppressed (including patients prescribed other immunosuppressive drugs e.g. glucocorticoids, NSAIDS)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Subject enrolment will undergo an initial screen for eligibility. During the screening evaluation the following procedures will be conducted and recorded for all patients:
- Complete medical/surgical history
- Patient’s suitability assessed against inclusion and exclusion criteria
- Record relevant prior and concomitant medications
- Haematology and Chemistry
- Serology for HIV, hepatitis B and C
- 10-20mls of peripheral blood
- Full physical examination
- Vital signs and if available beforehand but not necessary -
- CT/MRI brain scans or SPECT of Head region as part of initial exam performed within several months prior to Day 1.
- Baseline MMSE < 10-20.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Nonrandomised trial
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Eligible participants will be assigned a subject ID to protect their identity. Data collected for scientific analysis will be de-identified.
Phase
Phase 1
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 285831 0
Charities/Societies/Foundations
Name [1] 285831 0
Royal Freemasons' Benevolent Institution
Address [1] 285831 0
P.O. Box A2019
Sydney South
NSW 1235
Country [1] 285831 0
Australia
Primary sponsor type
University
Name
Griffith University
Address
170 Kessels Road
Nathan
QLD 4111
Country
Australia
Secondary sponsor category [1] 284655 0
None
Name [1] 284655 0
Address [1] 284655 0
Country [1] 284655 0
Other collaborator category [1] 277025 0
Hospital
Name [1] 277025 0
Gold Coast Hospital
Address [1] 277025 0
108 Nerang Street
Southport
QLD 4215
Country [1] 277025 0
Australia
Other collaborator category [2] 277027 0
Individual
Name [2] 277027 0
Dr Bradley Ng
Address [2] 277027 0
Robina Hospital
Older Persons Mental Health
2 Bayberry Lane
Robina
QLD 4226
Country [2] 277027 0
Australia
Other collaborator category [3] 277028 0
Individual
Name [3] 277028 0
Dr Andrew Weissenberger
Address [3] 277028 0
Hope Island Medical Centre
10 Santa Barbara Road
Hope Island
QLD 4212
Country [3] 277028 0
Australia
Other collaborator category [4] 277029 0
Individual
Name [4] 277029 0
Dr Ventzislav Bonev
Address [4] 277029 0
Gold Coast Hospital
108 Nerang Street
Southport
QLD 4215
Country [4] 277029 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287854 0
Griffith University Human Research Ethics Committee
Ethics committee address [1] 287854 0
170 Kessels Road
Nathan
QLD 4111
Ethics committee country [1] 287854 0
Australia
Date submitted for ethics approval [1] 287854 0
Approval date [1] 287854 0
23/06/2011
Ethics approval number [1] 287854 0
MSC/06/10/HREC

Summary
Brief summary
Etanercept, when given by injection overlying the spine, has been reported to be very beneficial for treatment of patients with moderate Alzheimer’s disease and is a beneficial treatment for other related forms of dementia in multiple published, peer-reviewed scientific studies. The primary aim of the study is to determine the safety and tolerability of perispinal injection of Etanercept in subjects with progressive dementia with a focus on Australian Alzheimer's sufferers.
Trial website
http://www.griffith.edu.au/health/griffith-health-institute/research/alzheimers-trial
Trial related presentations / publications
References
1. Tobinick, E., Tumour necrosis factor modulation for treatment of Alzheimer's disease: rationale and current evidence. CNS Drugs, 2009. 23(9): p. 713-25.
2. Tobinick, E., Perispinal etanercept for neuroinflammatory disorders. Drug Discov Today, 2009. 14(3-4): p. 168-77.
3. Tobinick, E.L. and H. Gross, Rapid cognitive improvement in Alzheimer's disease following perispinal etanercept administration. J Neuroinflammation, 2008. 5: p.2.
4. Tobinick, E.L. and H. Gross, Rapid improvement in verbal fluency and aphasia following perispinal etanercept in Alzheimer's disease. BMC Neurol, 2008. 8: p.27.
5. Tobinick, E., Perispinal etanercept produces rapid improvement in primary progressive aphasia: identification of a novel, rapidly reversible TNF-mediated pathophysiologic mechanism. Medscape J Med, 2008. 10(6): p. 135.
6. Griffin, W.S., Perispinal etanercept: potential as an Alzheimer therapeutic. J Neuroinflammation, 2008. 5: p. 3.
7. Tobinick, E., Perispinal etanercept for treatment of Alzheimer's disease. Curr Alzheimer Res, 2007. 4(5): p. 550-2.
8. Tobinick, E., H. Gross, A. Weinberger, and H. Cohen, TNF-alpha modulation for treatment of Alzheimer's disease: a 6-month pilot study. MedGenMed, 2006. 8(2): p. 25.
Public notes

Contacts
Principal investigator
Name 34518 0
Address 34518 0
Country 34518 0
Phone 34518 0
Fax 34518 0
Email 34518 0
Contact person for public queries
Name 17765 0
Dr Shirley Wee
Address 17765 0
School of Medical Science
Griffith University
Gold Coast campus
Parklands Drive
Southport
QLD 4215
Country 17765 0
Australia
Phone 17765 0
+61-7-55528583
Fax 17765 0
+61-7-55528908
Email 17765 0
alzheimers-trial@griffith.edu.au
Contact person for scientific queries
Name 8693 0
Associate Professor Stephen Ralph
Address 8693 0
School of Medical Science
Griffith University
Gold Coast campus
Parklands Drive
Southport
QLD 4215
Country 8693 0
Australia
Phone 8693 0
+61-7-55528583
Fax 8693 0
+61-7-55528908
Email 8693 0
s.ralph@griffith.edu.au

No information has been provided regarding IPD availability
Summary results
No Results