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

Study Type:	Interventional
Study Design:	Primary Purpose: Treatment

Resource links provided by NLM:

Genetics Home Reference related topics: MECP2 duplication syndrome PPM-X syndrome Renpenning syndrome Rett syndrome

MedlinePlus related topics: Rett Syndrome

Drug Information available for: Dextromethorphan hydrobromide Dextromethorphan Topiramate Donepezil hydrochloride Donepezil

U.S. FDA Resources

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.

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

Keywords provided by Office of Rare Diseases (ORD):

Rett syndrome
neurologic and psychiatric disorders
rare disease

Additional relevant MeSH terms:

Rett Syndrome
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Nervous System Diseases
Mental Retardation, X-Linked
Mental Retardation
Neurobehavioral Manifestations
Neurologic Manifestations
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Dextromethorphan
Topiramate
Donepezil
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents

Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Antitussive Agents
Central Nervous System Agents
Therapeutic Uses
Respiratory System Agents
Anticonvulsants
Neuroprotective Agents
Protective Agents
Anti-Obesity Agents
Cholinesterase Inhibitors
Enzyme Inhibitors
Cholinergic Agents

ClinicalTrials.gov processed this record on May 21, 2013