Study of the Pathogenesis of Rett Syndrome - Full Text View

Purpose

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 of cholinergic drugs based on preliminary evidence for reduced levels of brain acetylcholine, while continuing supportive care to modify seizures, respiratory abnormalities, and motor disturbances, and improve nutrition, behavior, and learning.

IV. Identify targets for future therapeutic interventions, e.g., growth factors, to influence neurologic recovery.

Condition	Intervention
Rett Syndrome	Drug: dextromethorphan Drug: topiramate Drug: Donepezil

Genetics Home Reference related topics:

familial encephalopathy with neuroserpin inclusion bodies L1 syndrome Rett syndrome

MedlinePlus related topics:

Rett Syndrome

Drug Information available for:

Topiramate Donepezil E 2020 Dextromethorphan Dextromethorphan hydrobromide Levomethorphan Racemethorphan

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment

Further study details as provided by Office of Rare Diseases (ORD):

Estimated Enrollment:	120
Study Start Date:	January 1995

Detailed Description:

PROTOCOL OUTLINE: Patients receive a comprehensive clinical evaluation including an ophthalmologic exam; speech, communication, and developmental assessment; nutritional evaluation; neurologic exam; respiratory monitoring; and cytogenetic studies.

Selected patients with malnutrition are given night feedings of Pediasure with Fiber by nasogastric tube. Specific recommendations for feeding techniques and diet are made.

Selected patients with seizures or severe hyperventilation and progressive rigidity are nonrandomly assigned to dextromethorphan or topiramate therapy.

Oral dextromethorphan is maintained 6 months to 1 year; duration of therapy depends on response. Oral topiramate is given for 6 months to 1 year, and Aricept for 6 months to 1 year.

Concurrent anticonvulsants may require dose adjustments while on above protocols. Supportive care for constipation, scoliosis, and weight loss is allowed.

Eligibility

Ages Eligible for Study:	up to 45 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

PROTOCOL ENTRY CRITERIA:

Rett syndrome

Diagnosis confirmed on study

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004807

Sponsors and Collaborators

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

Johns Hopkins University

Investigators


Study Chair:	Sakkubai Naidu	Johns Hopkins University

More Information

Publications:

Wenk GL, Naidu S, Casanova MF, Kitt CA, Moser H. Altered neurochemical markers in Rett's syndrome. Neurology. 1991 Nov;41(11):1753-6.

Reiss AL, Faruque F, Naidu S, Abrams M, Beaty T, Bryan RN, Moser H. Neuroanatomy of Rett syndrome: a volumetric imaging study. Ann Neurol. 1993 Aug;34(2):227-34.

Wenk GL, O'Leary M, Nemeroff CB, Bissette G, Moser H, Naidu S. Neurochemical alterations in Rett syndrome. Brain Res Dev Brain Res. 1993 Jul 16;74(1):67-72.

Cooke DW, Naidu S, Plotnick L, Berkovitz GD. Abnormalities of thyroid function and glucose control in subjects with Rett syndrome. Horm Res. 1995;43(6):273-8.

Naidu S, Hyman S, Harris EL, Narayanan V, Johns D, Castora F. Rett syndrome studies of natural history and search for a genetic marker. Neuropediatrics. 1995 Apr;26(2):63-6.

Naidu S, Hyman S, Piazza K, Savedra J, Perman J, Wenk G, Kitt C, Troncoso J, Price D, Cassanova M, et al. The Rett syndrome: progress report on studies at the Kennedy Institute. Brain Dev. 1990;12(1):5-7.

Casanova MF, Naidu S, Goldberg TE, Moser HW, Khoromi S, Kumar A, Kleinman JE, Weinberger DR. Quantitative magnetic resonance imaging in Rett syndrome. J Neuropsychiatry Clin Neurosci. 1991 Winter;3(1):66-72.

Naidu S, Wong DF, Kitt C, Wenk G, Moser HW. Positron emission tomography in the Rett syndrome: clinical, biochemical and pathological correlates. Brain Dev. 1992 May;14 Suppl:S75-9.

Marcus CL, Carroll JL, McColley SA, Loughlin GM, Curtis S, Pyzik P, Naidu S. Polysomnographic characteristics of patients with Rett syndrome. J Pediatr. 1994 Aug;125(2):218-24.

Study ID Numbers:	199/12009, JHUSM-KKI-87021203
First Received:	February 24, 2000
Last Updated:	June 23, 2005
ClinicalTrials.gov Identifier:	NCT00004807
Health Authority:	United States: Federal Government

Keywords provided by Office of Rare Diseases (ORD):

Rett syndrome

neurologic and psychiatric disorders

rare disease

Study placed in the following topic categories:

Developmental Disabilities

Excitatory Amino Acids

Rett syndrome

Rare Diseases

Neurodegenerative Diseases

Naphazoline

Mental Retardation

Child Development Disorders, Pervasive

Oxymetazoline

Rett Syndrome

Heredodegenerative Disorders, Nervous System

Genetic Diseases, Inborn

Guaifenesin

Phenylephrine

Mental Disorders

Donepezil

Mental Disorders Diagnosed in Childhood

Dextromethorphan

Genetic Diseases, X-Linked

Topiramate

Neurologic Manifestations

Phenylpropanolamine

Neurobehavioral Manifestations

Additional relevant MeSH terms:

Respiratory System Agents

Neurotransmitter Agents

Disease

Molecular Mechanisms of Pharmacological Action

Nervous System Diseases

Physiological Effects of Drugs

Excitatory Amino Acid Agents

Protective Agents

Neuroprotective Agents

Pharmacologic Actions

Anti-Obesity Agents

Pathologic Processes

Therapeutic Uses

Syndrome

Mental Retardation, X-Linked

Antitussive Agents

Central Nervous System Agents

Anticonvulsants

Excitatory Amino Acid Antagonists

ClinicalTrials.gov processed this record on December 03, 2008

Sponsors and Collaborators:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Johns Hopkins University
Information provided by:	Office of Rare Diseases (ORD)
ClinicalTrials.gov Identifier:	NCT00004807