Diffusion Tensor Weighted MRI in Alzheimer's Disease Modifying Treatment Effects of Galantamine (Reminyl®) - Full Text View

Purpose

Alzheimer's disease (AD) is characterized by progressive subcortical and cortical neuronal degeneration. AD patients differ in the time course of neuronal degeneration and accompanying cognitive decline.

With recent advances in MR imaging, including optimized data acquisition and processing techniques, tools that are especially well suited for tracking long-term pathological changes as well as drug treatment effects have become available. In addition to structural imaging, new acquisition and analysis techniques have been developed to determine integrity of subcortical fiber tracts in vivo.

In the present project we propose to determine predictors of disease progression and treatment response and investigate potential treatment effects on structural disease progression, covering the continuum from axonal degeneration to cortical neuronal loss taking advantage of recent advances in MRI acquisition and analysis techniques.

Condition	Intervention	Phase
Alzheimer's Disease	Drug: Galantamine (Reminyl®) Drug: Placebo/Galantamine (Reminyl®)	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	Diffusion Tensor Weighted MRI in Alzheimer's Disease: Prediction and Mapping of Symptomatic and Disease Modifying Treatment Effects of Galantamine (Reminyl®)

Resource links provided by NLM:

Genetics Home Reference related topics: Alzheimer disease

MedlinePlus related topics: Alzheimer's Disease

Drug Information available for: Galantamine Galantamine hydrobromide

Genetic and Rare Diseases Information Center resources: Familial Alzheimer Disease

U.S. FDA Resources

Further study details as provided by Ludwig-Maximilians - University of Munich:


Estimated Enrollment:	20
Study Start Date:	September 2006
Estimated Study Completion Date:	September 2008

Arms	Assigned Interventions
Active Comparator: 1	Drug: Galantamine (Reminyl®) 8mg - 24mg
Placebo Comparator: 2	Drug: Placebo/Galantamine (Reminyl®) Patients are treated double-blind with placebo for 6 months, followed by treatment with Galantamine (Reminyl®) for another 6 months. Dose scheme: 8mg-24mg

Detailed Description:

The outlined project will provide data to determine the value of cortical and subcortical volumetric and diffusion markers of neuronal degeneration to predict disease progression and response to (acetyl-)cholinergic treatment with Galantamine (Reminyl®). Furthermore, analysis of longitudinal MRI data in respect to cortical and subcortical atrophy and fiber degeneration will provide an estimate of the potential of new MRI analysis techniques to determine effects of (acetyl-)cholinergic treatment on rates of disease progression. Finally, the proposed study will allow determining the potential value of a new MRI technique, diffusion tensor imaging, to show the morphological correlate of cortical disconnection in AD and to map progression and treatment related effects on subcortical fiber tract integrity in AD.

The major scientific value of this project is the combined description of the effect of Galantamine (Reminyl®) on disease progression on the structural level of analysis in AD. The data from this project may help to identify predictors of treatment response and to elucidate the mechanisms of drug action of Galantamine (Reminyl®) in AD.

Eligibility


Ages Eligible for Study:	55 Years to 95 Years (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

male of female patients aged ≥ 55years, fulfilling criteria of the National Institute of Neurological and Communicative Disease and Stroke (NINCDS) and the Alzheimer's Disease and Related Disorders Association (ADRDA) for the diagnosis of clinically probable AD
MMSE score > 16
no evidence for other psychiatric axis I disorders according to DSM- IV criteria
no evidence for cerebrovascular disease (radiological confirmed), cardiac or cerebral infarct (three months before the study), thyroid disease and other neurodegenerative or neuroinflammatory disorders. No evidence for acute or unstable medical condition.
no risk factors of hypertension, cardiac disease (e.g. angina pectoris, congestive heart failure, right bundle branch block, or arrhythmias), diabetes mellitus (stable within 3 months)
no history of drug/alcohol abuse
no history of panic attacks or claustrophobia (due to requirements of the MRI examinination)
no surgical implants or non-fixed metallic particles
patient has not taken a previously approved cholinesterase inhibitor or memantine, which has been discontinued at least 6 weeks prior to the Screening
patient is able to provide written Informed Consent to participate study. If, at investigator's discretion, a patient is considered not to be capable to give legal consent, then written consent must also be obtained from the patient's legally acceptable representative.

Exclusion Criteria:

no evidence of memory or other cognitive impairments, verified by clinical history and cognitive testing
previous or current history of degenerative or ischemic disorders of the peripheral or central nervous system
previous or current history of systemic disorders
no ability to participate and no willing to give informed consent and comply with the study restrictions
MMSE score < 16 range

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00523666

Contacts


Contact: Stefan Teipel, MD	+498951605860	stefan.teipel@med.uni-muenchen.de
Contact: Harald Hampel, MD		harald.hampel@med.uni-muenchen.de

Locations


Germany
Ludwig-Maximilian University of Munich	Recruiting
Munich, Germany, D-80336
Principal Investigator: Stefan Teipel, MD
Sub-Investigator: Djyldyz Sydykova, MD

Sponsors and Collaborators

Ludwig-Maximilians - University of Munich

Investigators


Study Director:	Harald Hampel, MD	Dementia Research Section and Memory Clinic, Department of Psychiatry, Nussbaumstrasse 7, 80336 Munich, Germany
Principal Investigator:	Stefan Teipel, MD	Dementia Research Section and Memory Clinic, Department of Psychiatry, Nussbaumstrasse 7, 80336 Munich, Germany

More Information

Publications:

Teipel SJ, Stahl R, Dietrich O, Schoenberg SO, Perneczky R, Bokde AL, Reiser MF, Möller HJ, Hampel H. Multivariate network analysis of fiber tract integrity in Alzheimer's disease. Neuroimage. 2007 Feb 1;34(3):985-95. Epub 2006 Dec 12.

Sydykova D, Stahl R, Dietrich O, Ewers M, Reiser MF, Schoenberg SO, Möller HJ, Hampel H, Teipel SJ. Fiber connections between the cerebral cortex and the corpus callosum in Alzheimer's disease: a diffusion tensor imaging and voxel-based morphometry study. Cereb Cortex. 2007 Oct;17(10):2276-82. Epub 2006 Dec 12.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Blautzik J, Keeser D, Paolini M, Kirsch V, Berman A, Coates U, Reiser M, Teipel SJ, Meindl T. Functional connectivity increase in the default-mode network of patients with Alzheimer's disease after long-term treatment with Galantamine. Eur Neuropsychopharmacol. 2016 Mar;26(3):602-13. doi: 10.1016/j.euroneuro.2015.12.006. Epub 2015 Dec 10.


ClinicalTrials.gov Identifier:	NCT00523666 History of Changes
Other Study ID Numbers:	DTI001 EudraCT 2005-003762-41
Study First Received:	August 29, 2007
Last Updated:	August 29, 2007
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Ludwig-Maximilians - University of Munich:


Alzheimer's disease diffusion tensor imaging

Additional relevant MeSH terms:


Alzheimer Disease Dementia Brain Diseases Central Nervous System Diseases Nervous System Diseases Tauopathies Neurodegenerative Diseases Neurocognitive Disorders Mental Disorders Galantamine	Cholinesterase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Cholinergic Agents Neurotransmitter Agents Physiological Effects of Drugs Parasympathomimetics Autonomic Agents Peripheral Nervous System Agents Nootropic Agents

ClinicalTrials.gov processed this record on September 23, 2016