Memantine and Down's Syndrome
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|ClinicalTrials.gov Identifier: NCT00240760|
Recruitment Status : Unknown
Verified October 2005 by King's College London.
Recruitment status was: Recruiting
First Posted : October 18, 2005
Last Update Posted : February 20, 2006
|First Submitted Date ICMJE||October 14, 2005|
|First Posted Date ICMJE||October 18, 2005|
|Last Update Posted Date||February 20, 2006|
|Study Start Date ICMJE||October 2005|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE
|Change History||Complete list of historical versions of study NCT00240760 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Memantine and Down's Syndrome|
|Official Title ICMJE||Efficacy and Safety of Memantine Hydrochloride, a Low Affinity Antagonist to N-Methyl-D-Aspartate (NMDA) Type Receptors, in the Prevention of Cognitive Decline and Disease Progression in Down’s Syndrome|
This is a study to assess whether memantine is effective and safe in preventing age related cognitive deterioration and dementia in people with Down's syndrome (DS) age 40 and over. The study will last for a year and it will include 180 people with Down's syndrome with and without dementia. Participants will be assessed on memory skills, attention and problem solving abilities. Quality of life and abilities for everyday living skills will also be regularly checked.
Biochemical and pathological:
Biochemical and pathological:
Over the age of 40, all people with Down’s Syndrome have substantial changes in the brain similar to those of Alzheimer’s disease and most are at very high risk of developing a clinical dementia with progressive decline of function and cognitive abilities.
There are changes to all of the key chemical messenger systems in the brain as people develop Alzheimer’s disease. One of the most ubiquitous chemical messenger systems, present on the majority of nerve cells in the brain, is called the glutamatergic system. In this system the main receptors present on the nerve endings are referred to as glutamate receptors. Under certain circumstances, usually when there is damage to particular parts of the brain, these receptors can lead to “overfiring” of the nerve cells with disastrous consequences. This can result in the generation of a number of toxic chemical molecules that lead to further damage to the nerve cells (such as phopholipases, proteases, nitric oxide synthases, inflammatory molecules and free radicals), usually referred to as excitotoxicity. Memantine blocks the effects of pathologically elevated tonic levels of glutamate that may lead to dysfunction of nerve cells and in this way is thought to block the main glutamate excitotoxicity site on nerve cells.
Randomized clinical trials in people with Alzheimer’s disease indicate that memantine significantly slows down the progression of functional and cognitive impairments. Memantine has now been licensed for the treatment of moderate-severe Alzheimer’s disease on the basis of these trials. We would hypothesise that older people with Down’s syndrome would particularly benefit from treatment with Memantine, partly because of the large amount of Alzheimer’s disease changes present in the brain and partly because excessive glutamate receptor activity has been demonstrated in adults with Down’s syndrome.
In a recent study we assessed 122 individuals with Down’s Syndrome using newly developed neuropsychometric battery of tests, (the the Down's syndrome Attention, Memory and Executive function battery -DAME battery, Margallo-Lana 2002a,b). People with Down’s Syndrome over the age of 40 without dementia experienced a decline of 11% over one year, indicating that progressive cognitive decline precedes dementia (hence offering an important opportunity for prevention) and that these measurements are sensitive to cognitive change over time, hence a trial to evaluate the prevention of dementia is feasible with current evaluation measures.
Participants will be given Memantine or placebo (dummy tablet) for 52 weeks. To avoid bias, participants will be allocated to the placebo or Memantine group at random (this is a randomized trial) and none of the researchers or participants will know which treatment people are getting (the study is double blind). However, in an emergency, the investigators can contact the study pharmacist to find out whether a particular participant was receiving Memantine or the dummy tablet. The placebo and Memantine groups will be compared at the end of the study (the study is placebo control) to see if Memantine is any better than the dummy pill. The efficacy of Memantine will be assessed by comparing the change in scores between the initial assessments and assessments in the follow-up period at 12, 26 and 52 weeks. Thus participant will be assessed on 4 occasions.
In addition to a clinical history and the collection of standardized information such as any adverse events, the assessment will include:
180 people aged > 40 with DS (with or without dementia) who have mild-moderate learning disability, in a double blind, placebo controlled design.
Related Biochemical Studies:
Blood samples (10ml) will be taken at baseline and the final follow-up assessment. Blood will be processed to yield four different components: plasma, platelets, red and white blood cells.
Plasma concentrations of the amino acid neurotransmitters aspartate and glutamate will be measured together with the rate of uptake of glutamate into blood cells (platelets). The ability of glutamate to bind to the platelets' receptors (particularly the NMDA receptor - a sub-type of glutamate receptor) will also be also assessed. These investigations will determine whether Memantine protects and modulates glutamatergic transmission.
Plasma concentrations amyloid (Abeta species 1-40/1-42), the protein that typically accumulates in the brains of people with Alzheimer's disease, will also be measured together with plasma concentrations of the amyloid precursor protein (APP). Preliminary studies will be also undertaken to see if glutamate receptors in platelets (NMDA receptors) regulate the release of APP/Abeta.
The study will also investigate genetic factors that may affect the risk of Alzheimer's disease in people with Down's Syndrome. Any identified genetic factors will be examined to see if they can predict response to treatment.
These investigations will help to determine if Memantine alters the accumulation of proteins in the brain typical of Alzheimer's disease in people with Down's syndrome.
Consumers panels of relatives of people with DS and carers have been involved in protocol development and the writing of information sheets.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Not Applicable|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
|Intervention ICMJE||Drug: Memantine Hydrochloride|
|Study Arms ICMJE||Not Provided|
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Unknown status|
|Original Enrollment ICMJE||Same as current|
|Study Completion Date ICMJE||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
Inclusion criteria will be:
Exclusion criteria will be:
|Ages ICMJE||18 Years and older (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United Kingdom|
|Removed Location Countries|
|NCT Number ICMJE||NCT00240760|
|Other Study ID Numbers ICMJE||KCL/DS/MEM/1
EUDRACT- 2005 000381 39
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||King's College London|
|Collaborators ICMJE||Not Provided|
|PRS Account||King's College London|
|Verification Date||October 2005|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP