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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]

Nil

Universal Trial Number (UTN)

U1111-1133-1715

Trial acronym

Nil

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Dementia

Condition category

Condition code

Mental Health

Other mental health disorders

Neurological

Dementias

Inflammatory and Immune System

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]

Treatment: Drugs

Comparator / control treatment

None

Control group

Uncontrolled

Outcomes

Primary outcome [1]

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]

Post-intervention observation over a 2-hour period.

Primary outcome [2]

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]

a) Pre-intervention (Baseline)
b) Post-intervention (weekly)
c) Follow-up (at the end of 4 weeks treatment)

Secondary outcome [1]

Measure of serum change in inflammatory biomarkers by blood sample profile.

Timepoint [1]

a) Pre-invention (Baseline)
b) Post-invention (weekly)
c) Follow-up (at the end of 4 weeks treatment)

Secondary outcome [2]

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]

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

Sex

Both males and females

Can healthy volunteers participate?

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

1/10/2012

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]

Charities/Societies/Foundations

Name [1]

Royal Freemasons' Benevolent Institution

Address [1]

P.O. Box A2019
Sydney South
NSW 1235

Country [1]

Australia

Primary sponsor type

University

Name

Griffith University

Address

170 Kessels Road
Nathan
QLD 4111

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Other collaborator category [1]

Hospital

Name [1]

Gold Coast Hospital

Address [1]

108 Nerang Street
Southport
QLD 4215

Country [1]

Australia

Other collaborator category [2]

Individual

Name [2]

Dr Bradley Ng

Address [2]

Robina Hospital
Older Persons Mental Health
2 Bayberry Lane
Robina
QLD 4226

Country [2]

Australia

Other collaborator category [3]

Individual

Name [3]

Dr Andrew Weissenberger

Address [3]

Hope Island Medical Centre
10 Santa Barbara Road
Hope Island
QLD 4212

Country [3]

Australia

Other collaborator category [4]

Individual

Name [4]

Dr Ventzislav Bonev

Address [4]

Gold Coast Hospital
108 Nerang Street
Southport
QLD 4215

Country [4]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Griffith University Human Research Ethics Committee

Ethics committee address [1]

170 Kessels Road
Nathan
QLD 4111

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

23/06/2011

Ethics approval number [1]

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

Address

Country

Phone

Fax

Contact person for public queries

Name

Dr Shirley Wee

Address

School of Medical Science
Griffith University
Gold Coast campus
Parklands Drive
Southport
QLD 4215

Country

Australia

Phone

+61-7-55528583

Fax

+61-7-55528908

alzheimers-trial@griffith.edu.au

Contact person for scientific queries

Name

Associate Professor Stephen Ralph

Address

School of Medical Science
Griffith University
Gold Coast campus
Parklands Drive
Southport
QLD 4215

Country

Australia

Phone

+61-7-55528583

Fax

+61-7-55528908

s.ralph@griffith.edu.au

No information has been provided regarding IPD availability

What supporting documents are/will be available?

Current supporting documents:

Updated to:

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
23231	Other	Clark IA. Randomized controlled trial validating the use of perispinal etanercept to reduce post-stroke disability has wide-ranging implications. Expert Rev Neurother. 2020 Mar;20(3):203-205. doi: 10.1080/14737175.2020.1727742. Epub 2020 Feb 13. PMID: 32028804.
23828	Other				De-identified data files can be made available on ... [More Details]

Results publications and other study-related documents

Documents added manually

Current Study Results

No documents have been uploaded by study researchers.

Update to Study Results

Doc. No.	Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
3935	Plain language summary	No		Perispinal etanercept can provide significant and ... [More Details]
4374	Study results article	Yes		Ralph SJ, Weissenberger A, Bonev V, King LD, Bonha... [More Details]

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Perispinal Delivery of CNS Drugs.	2016	https://dx.doi.org/10.1007/s40263-016-0339-2

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

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