Clinical trial NCT00004807: Study of the Pathogenesis of Rett Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Rett Syndrome
Keywords: Rett syndrome
neurologic and psychiatric disorders
rare disease
Lead sponsor: Office of Rare Diseases (ORD)
Sponsor class: NIH
Collaborators: name: Johns Hopkins University
First posted: 2000-02-25
Enrollment: 120
Sex: ALL
Minimum age (years): 0
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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 criteria: PROTOCOL ENTRY CRITERIA:

Rett syndrome

Diagnosis confirmed on study

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Johns Hopkins University
name: Sakkubai Naidu
role: STUDY_CHAIR
References:
citation: Wenk GL, Naidu S, Casanova MF, Kitt CA, Moser H. Altered neurochemical markers in Rett's syndrome. Neurology. 1991 Nov;41(11):1753-6. doi: 10.1212/wnl.41.11.1753.
citation: 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. doi: 10.1002/ana.410340220.
citation: 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. doi: 10.1016/0165-3806(93)90084-n.
citation: 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. doi: 10.1159/000184309.
citation: 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. doi: 10.1055/s-2007-979724.
citation: 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. doi: 10.1016/s0387-7604(12)80164-1.
citation: 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. doi: 10.1176/jnp.3.1.66.
citation: 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.
citation: 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. doi: 10.1016/s0022-3476(94)70196-2.