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Alzheimer's DiseaseNCT02063269

Brain Changes by Rivastigmine According to Butyrylcholinesterase Alleles

A study testing Rivastigmine in people with Alzheimer's Disease, run by Seoul National University Hospital at 1 site in South Korea.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Butyrylcholinesterase (BuChE) activity is increasing in Alzheimer Disease (AD) process (Lane et al., 2006). BuChE wild type has stronger butyrylcholine esterase activity than BuChE K variant allele and this strong activity can affect AD brain negatively by choline depletion. Read more about this study

Who is it for?
Ages 55 to 80 years
Conditions the study is for
Alzheimer's Disease
What is being tested?
Rivastigmine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
1 siteSouth Korea
Study dates
Feb 2014to Jun 2017
Phase
Interventional
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 55 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Clinical diagnosis of Alzheimer's Disease (NINCD-ADRDA and MMSE between 10 ~26)
  • Who didn't take Cholinesterase Inhibitor on liver within 3 months

Who cannot join

  • diagnosed with diseases other than AD that affect brain atrophy according to Brain MRI
  • Diagnosed with diseases other than AD which affect cognitive functions (i.g. Schizophrenia, Major Depression, Mental Retardation, encephalopathy, etc.)
  • Didn't suspect of drug or alcohol addictions within last decade
  • Unable to participate the study due to poor sight and hearing
  • Who aren't suitable to participate according to the researchers' judgement

Trial locations and contacts

1 site in 1 country.

South Korea1 site

  • Seoul Metropolitan Government Seoul National University Boramae Medical Center

    Seoul, 156-707

Other trials in South Korea

About this study

Official title: Differences of Functional Changes in Brain by Rivastigmine According to Butyrylcholinesterase Alleles in Alzheimer's Disease Patients(Rivastigmine, Imaging, and BuChE in AD: RIBA)

Butyrylcholinesterase (BuChE) activity is increasing in Alzheimer Disease (AD) process (Lane et al., 2006). BuChE wild type has stronger butyrylcholine esterase activity than BuChE K variant allele and this strong activity can affect AD brain negatively by choline depletion. Rivastigmine has unique dual action - acetylcholine esterase inhibition and butyrylcholine esterase inhibition. Therefore, rivastigmine can lower serum butyrylcholine esterase activity and delay functional decrease of Fluorodeoxyglucose positron emission tomography (FDG PET) images in AD patients with BuChE wild type allele by strong BuChE inhibition.

It suggests that rivastigmine can affect brain function differently by BuChE genotype in AD. Therefore, we will try to find the different changes of serum butyrylcholine esterase activity by ELISA and functional and structural changes of brain between BuChE wild type and K-variant type by FDG PET and MRI pre and post images after 12 month use of rivastigmine.

  1. Primary objective:
  2. the mean changes of Standardized Uptake Values (SUVmean) in PET imaging
  3. the mean changes of serum BuChE activity between BuChE wild type and K-variant type.
  4. Secondary objectives:
  5. the mean changes of cortical thickness in brain MRI
  6. the cognitive changes in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog)
  7. the cognitive changes in Mini-Mental State Exam (MMSE)
  8. the daily function changes by Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
  9. the behavioural changes by Caregiver-Administered Neuropsychiatric Inventory (NPI)
  10. the disease severity changes by Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) between BuChE wild type and K-variant type.
Being tested
Rivastigmine
Keywords
rivastigmine, butyrylcholinesterase, MRI, PET
Medical subject headings
Alzheimer Disease, Butyrylcholinesterase deficiency

What participants receive

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

  • RivastigmineDrug

    Also called Exelon

    9-18mg/rivastigmine for 52 weeks

Study groups in NCT02063269
Study groupRoleWhat they receive
RivastigmineExperimentalRivastigmine
Receives: Drug: Rivastigmine

What is being measured

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

  1. the mean changes of Standardized Uptake Values (SUVmean) in PET imaging

    Unit: mg/100g/min

    Measured: screening and 52weeks (2 times)

  2. the mean changes of serum BuChE activity between BuChE wild type and K-variant type

    unit of umil ACSCh/h/mg

    Measured: screening and 52weeks (2 times)

Secondary outcomes (6)

  1. the mean changes of cortical thickness in brain MRI

    unit of mm

    Measured: screening and 52weeks (2 times)

  2. the cognitive changes in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog)

    unit in points

    Measured: screening, 26, and 52 weeks (3 times)

  3. the cognitive changes in Mini-Mental State Exam (MMSE)

    unit in points

    Measured: screening, 26, and 52 weeks (3 times)

  4. the daily function changes by Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)

    unit in points

    Measured: screening, 26, and 52 weeks (3 times)

  5. the behavioural changes by Caregiver-Administered Neuropsychiatric Inventory (NPI)

    unit in points

    Measured: screening, 26, and 52 weeks (3 times)

  6. the disease severity changes by Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) between BuChE wild type and K-variant type

    unit in points

    Measured: screening, 26, and 52 weeks (3 times)

Timeline

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

  1. First posted14 Feb 2014 (estimated)
  2. Study startFeb 2014
  3. Primary completionJun 2017 (estimated)
  4. Study completionJun 2017 (estimated)

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 N/A
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
70 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02063269
Sponsor's protocol ID
CENA713DKR15T
Status last verified
May 2015
First submitted
12 Feb 2014
Last updated
14 May 2015
Results posted
No
Data monitoring committee
Yes

Publications

  • Ames A 3rd. CNS energy metabolism as related to function. Brain Res Brain Res Rev. 2000 Nov;34(1-2):42-68. doi: 10.1016/s0165-0173(00)00038-2.

    PubMed 11086186

  • Blesa R, Bullock R, He Y, Bergman H, Gambina G, Meyer J, Rapatz G, Nagel J, Lane R. Effect of butyrylcholinesterase genotype on the response to rivastigmine or donepezil in younger patients with Alzheimer's disease. Pharmacogenet Genomics. 2006 Nov;16(11):771-4. doi: 10.1097/01.fpc.0000220573.05714.ac.

    PubMed 17047484

  • Davies P, Maloney AJ. Selective loss of central cholinergic neurons in Alzheimer's disease. Lancet. 1976 Dec 25;2(8000):1403. doi: 10.1016/s0140-6736(76)91936-x. No abstract available.

    PubMed 63862

  • Fox MD, Raichle ME. Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci. 2007 Sep;8(9):700-11. doi: 10.1038/nrn2201.

    PubMed 17704812

  • Holmes C, Ballard C, Lehmann D, David Smith A, Beaumont H, Day IN, Nadeem Khan M, Lovestone S, McCulley M, Morris CM, Munoz DG, O'Brien K, Russ C, Del Ser T, Warden D. Rate of progression of cognitive decline in Alzheimer's disease: effect of butyrylcholinesterase K gene variation. J Neurol Neurosurg Psychiatry. 2005 May;76(5):640-3. doi: 10.1136/jnnp.2004.039321.

    PubMed 15834019

  • Kimura N, Kumamoto T, Masuda T, Hanaoka T, Okazaki T, Arakawa R. Evaluation of the regional cerebral blood flow changes during long-term donepezil therapy in patients with Alzheimer's disease using 3DSRT. J Neuroimaging. 2012 Jul;22(3):299-304. doi: 10.1111/j.1552-6569.2011.00612.x. Epub 2011 Jun 23.

    PubMed 21699607

  • Lane RM, Potkin SG, Enz A. Targeting acetylcholinesterase and butyrylcholinesterase in dementia. Int J Neuropsychopharmacol. 2006 Feb;9(1):101-24. doi: 10.1017/S1461145705005833. Epub 2005 Aug 5.

    PubMed 16083515

  • Levy JA, Parasuraman R, Greenwood PM, Dukoff R, Sunderland T. Acetylcholine affects the spatial scale of attention: evidence from Alzheimer's disease. Neuropsychology. 2000 Apr;14(2):288-98. doi: 10.1037//0894-4105.14.2.288.

    PubMed 10791868

  • Nobili F, Koulibaly M, Vitali P, Migneco O, Mariani G, Ebmeier K, Pupi A, Robert PH, Rodriguez G, Darcourt J. Brain perfusion follow-up in Alzheimer's patients during treatment with acetylcholinesterase inhibitors. J Nucl Med. 2002 Aug;43(8):983-90.

    PubMed 12163621

  • O'Brien KK, Saxby BK, Ballard CG, Grace J, Harrington F, Ford GA, O'Brien JT, Swan AG, Fairbairn AF, Wesnes K, del Ser T, Edwardson JA, Morris CM, McKeith IG. Regulation of attention and response to therapy in dementia by butyrylcholinesterase. Pharmacogenetics. 2003 Apr;13(4):231-9. doi: 10.1097/00008571-200304000-00008.

    PubMed 12668920

  • Poirier J. Evidence that the clinical effects of cholinesterase inhibitors are related to potency and targeting of action. Int J Clin Pract Suppl. 2002 Jun;(127):6-19.

    PubMed 12139368

  • Silverman JM, Ciresi G, Smith CJ, Marin DB, Schnaider-Beeri M. Variability of familial risk of Alzheimer disease across the late life span. Arch Gen Psychiatry. 2005 May;62(5):565-73. doi: 10.1001/archpsyc.62.5.565.

    PubMed 15867110

  • Ki CS, Na DL, Kim JW, Kim HJ, Kim DK, Yoon BK. No association between the genes for butyrylcholinesterase K variant and apolipoprotein E4 in late-onset Alzheimer's disease. Am J Med Genet. 1999 Apr 16;88(2):113-5. doi: 10.1002/(sici)1096-8628(19990416)88:23.0.co;2-3.

    PubMed 10206226

  • Kim KW, Jhoo JH, Lee JH, Lee KU, Lee DY, Youn JC, Youn JY, Woo JI. Neither the butyrylcholinesterase K variant nor transferrin C2 variant confers a risk for Alzheimer's disease in Koreans. J Neural Transm (Vienna). 2001;108(10):1159-66. doi: 10.1007/s007020170005.

    PubMed 11725818

  • Jagust WJ, Bandy D, Chen K, Foster NL, Landau SM, Mathis CA, Price JC, Reiman EM, Skovronsky D, Koeppe RA; Alzheimer's Disease Neuroimaging Initiative. The Alzheimer's Disease Neuroimaging Initiative positron emission tomography core. Alzheimers Dement. 2010 May;6(3):221-9. doi: 10.1016/j.jalz.2010.03.003.

    PubMed 20451870

Questions about this trial

What is this clinical trial studying?

A study testing Rivastigmine in people with Alzheimer's Disease, run by Seoul National University Hospital at 1 site in South Korea.

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 2 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 14 May 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in South Korea. 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.

Are results available for this study?

Results are not available in the source record.

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?

the mean changes of Standardized Uptake Values (SUVmean) in PET imaging (time frame: screening and 52weeks (2 times)). The study lists 2 primary outcomes in all. 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 NCT02063269, which also lists 15 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 14 May 2015.

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