Study of the Pathogenesis of Rett Syndrome

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

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 or disease	Intervention/treatment	Phase
Rett Syndrome	Drug: dextromethorphan; Drug: topiramate; Drug: Donepezil	Not Applicable

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Enrollment :	120 participants
Primary Purpose:	Treatment
Study Start Date :	January 1995

Arms and Interventions

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Outcome Measures

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Eligibility Criteria

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	up to 45 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

PROTOCOL ENTRY CRITERIA:

Rett syndrome

Diagnosis confirmed on study

Contacts and Locations

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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

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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
First Posted:	February 25, 2000
Last Update Posted:	June 24, 2005
Last Verified:	December 1998

Keywords provided by Office of Rare Diseases (ORD):

Rett syndrome; neurologic and psychiatric disorders; rare disease

Additional relevant MeSH terms:

Syndrome; Rett Syndrome; Disease; Pathologic Processes; Mental Retardation, X-Linked; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Heredodegenerative Disorders, Nervous System; Donepezil; Dextromethorphan; Topiramate	Cholinesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Nootropic Agents; Anticonvulsants; Neuroprotective Agents; Protective Agents; Anti-Obesity Agents; Antitussive Agents; Respiratory System Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents