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Independent Studies of Dextromethorphan and of Donepezil Hydrochloride for Rett Syndrome

2014-08-27 03:54:53 | BioPortfolio

Summary

Rett syndrome (RTT) is a disorder in which the nervous system does not develop properly. RTT generally affects girls, but there are some boys who have been diagnosed with RTT. Symptoms of RTT include small brain size, poor language skills, repetitive hand movements, and seizures. This study will evaluate the effectiveness of two drugs in treating the symptoms of RTT.

Description

RTT is a neurodevelopmental disorder characterized by apparently normal early development followed by loss of purposeful hand use, distinctive hand stereotypies, slowed brain growth, loss of language, respiratory irregularities, GI disturbances, gait abnormalities, seizures, and mental retardation. These symptoms appear between ages 6 and 18 months (stage 2 of the disease) following apparently normal development (stage 1). Subsequently, there is gradual stabilization of severe mental retardation and motor compromise (stage 3). The majority (70% to 80%) of patients demonstrate mutations in the methyl-CpG-binding-protein-2 (MeCP2) gene, a transcription repressor located on chromosome Xq28. The disorder predominantly affects females, but a few males with mutations in MeCP2 have been identified, even though many of them do not have the classic symptoms recognized in females.

Recent studies demonstrate increased brain N-methyl-D-aspartate (NMDA) receptors in stages 2 and 3 of the disease. This age-specific increase in glutamate levels and their receptors contribute to brain damage. This first study will examine the effectiveness of dextromethorphan, an NMDA receptor antagonist, to ameliorate symptoms. Participants will be randomized to receive one of three doses of dextromethorphan. All participants will be admitted to the hospital for three days at the beginning of the study. During the hospitalization, participants will undergo physical exam, Dexascan, MRI, EEG, behavioral assessment, laboratory testing, and neuropsychological evaluations. Six months after baseline assessment, participants will be rehospitalized for 3 days for similar assessments.

Reduction in choline acetyltransferase activity in RTT patients may also contribute to disturbed cortical development and psychomotor retardation in RTT. Therefore, the second part of the study will evaluate the effect of donepezil hydrochloride, an inhibitor of acetylcholine-esterase, on acetylcholine levels. This portion of the study will not begin until pharmacokinetic data for donepezil in children is available.

Study Design

Allocation: Randomized, Control: Dose Comparison, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment

Conditions

Rett Syndrome

Intervention

dextromethorphan, donepezil hydrochloride

Location

Kennedy Krieger Institute
Baltimore
Maryland
United States

Status

Recruiting

Source

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:54:53-0400

Clinical Trials [1473 Associated Clinical Trials listed on BioPortfolio]

Study of the Pathogenesis of Rett Syndrome

OBJECTIVES: I. Extend current knowledge of the phenotype and natural history of Rett syndrome (RS). II. Continue the search for a cytogenetic and/or DNA marker. III. Study the effects o...

Trial of Dextromethorphan in Rett Syndrome

Increased brain glutamate and its NMDA receptors found in the brain of younger Rett syndrome (RTT) patients cause toxic damage to neurons (the brain's nerve cells), and contributing to EEG...

Evaluating The Safety Of Donepezil Hydrochloride (Aricept) For Up To 1 Year In The Treatment Of The Cognitive Dysfunction Exhibited By Children With Down Syndrome - Follow-Up To A 10-Week, Double-Blind, Placebo-Controlled Trial

The purpose of this study is to determine the safety of donepezil hydrochloride (Aricept) in children with Down syndrome who have finished the preceding 10-week, double-blind study of done...

Pharmacological Treatment of Rett Syndrome With Statins

This is a phase 2 , open label, dose escalating study of Lovastatin in Rett syndrome.

A Safety Study of NNZ-2566 in Pediatric Rett Syndrome

The purpose of this study is to determine whether NNZ-2566 is safe and well tolerated in the treatment of Rett syndrome in children and adolescents.

PubMed Articles [4911 Associated PubMed Articles listed on BioPortfolio]

Bone status in relation to ambulatory performance in girls with Rett syndrome: a 10-year longitudinal study.

Low bone mass is a frequent and early complication of girls with Rett syndrome. As a consequence of the low bone mass, Rett patients are at an increased risk of fragility fractures. This study aimed t...

Walking on treadmill with Rett syndrome-Effects on the autonomic nervous system.

People with Rett syndrome have deficient central autonomic control, which may interfere with walking. We have limited knowledge regarding the effects of exertion during physical activity in Rett syndr...

Neurophysiological and cognitive effects of Transcranial Direct Current Stimulation in three girls with Rett Syndrome with chronic language impairments.

this study was based on both neurophysiological decelerated activity and communication deficits in Rett Syndrome (RTT).

Rett syndrome from bench to bedside: recent advances.

Rett Syndrome is a severe neurological disorder mainly due to mutations in the methyl-CpG-binding protein 2 gene ( ). Mecp2 is known to play a role in chromatin organization and transcriptional regul...

Aerophagia and subcutaneous emphysema in a patient with Rett syndrome.

A patient with Rett syndrome presented to our Emergency Department with extensive subcutaneous emphysema in the cervical region, chest wall, upper extremities, and back. Diagnostic evaluation revealed...

Medical and Biotech [MESH] Definitions

A DNA-binding protein that interacts with methylated CPG ISLANDS. It plays a role in repressing GENETIC TRANSCRIPTION and is frequently mutated in RETT SYNDROME.

An inherited neurological developmental disorder that is associated with X-LINKED INHERITANCE and may be lethal in utero to hemizygous males. The affected female is normal until the age of 6-25 months when progressive loss of voluntary control of hand movements and communication skills; ATAXIA; SEIZURES; autistic behavior; intermittent HYPERVENTILATION; and HYPERAMMONEMIA appear. (From Menkes, Textbook of Child Neurology, 5th ed, p199)

A pharmaceutical preparation of sitagliptin phosphate and metformin hydrochloride that is used in the treatment of TYPE 2 DIABETES.

A piperazine derivative and PLATELET AGGREGATION INHIBITOR that is used to prevent THROMBOSIS in patients with ACUTE CORONARY SYNDROME; UNSTABLE ANGINA and MYOCARDIAL INFARCTION, as well as in those undergoing PERCUTANEOUS CORONARY INTERVENTIONS.

Dextro form of levorphanol. It acts as a noncompetitive NMDA receptor antagonist, among other effects, and has been proposed as a neuroprotective agent. It is also a metabolite of DEXTROMETHORPHAN.

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