Evidence map›Paper›PMID 28931647›Full record

Trial reportNeurology2017

Randomized open-label trial of dextromethorphan in Rett syndrome.

Constance L Smith-Hicks, Siddharth Gupta, Joshua B Ewen, Manisha Hong, Lisa Kratz, Richard Kelley, Elaine Tierney, Rebecca Vaurio, Genila Bibat, Abanti Sanyal and 4 more

Abstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neurology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 2 pooled it
3.7field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 44 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Sigma-1 receptor and seizures.Pharmacological research · 2023
    Review
  9. Targeting NMDA Receptor Complex in Management of Epilepsy.Pharmaceuticals (Basel, Switzerland) · 2022
    Review
  10. Review
  11. Article
  12. Review
  13. Breathing disturbances in Rett syndrome.Handbook of clinical neurology · 2022
    Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Drug Studies on Rett Syndrome: From Bench to Bedside.Journal of autism and developmental disorders · 2020
    Review
  20. Rett Syndrome and CDKL5 Deficiency Disorder: From Bench to Clinic.International journal of molecular sciences · 2019
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 1 institution in 1 country.

Constance L Smith-HicksFrom the Departments of Neurology (C.L.S.-H., S.G., J.B.E., M.V.J., S.N.), Psychological and Brain Science (J.B.E.), Pediatrics (L.K., R.K.), Psychiatry (E.T.), and Psychology (R.V.), and the Neurogenetics Department (G.B.), Kennedy Krieger Institute, Johns Hopkins University School of Medicine (N.B.); Investigational Drug Service, Department of Pharmacy (M.H.), Johns Hopkins Hospital; and Johns Hopkins Bloomberg School of Public Health (A.S., G.Y.), Johns Hopkins Biostatistics Center, Baltimore, MD.
Siddharth GuptaFrom the Departments of Neurology (C.L.S.-H., S.G., J.B.E., M.V.J., S.N.), Psychological and Brain Science (J.B.E.), Pediatrics (L.K., R.K.), Psychiatry (E.T.), and Psychology (R.V.), and the Neurogenetics Department (G.B.), Kennedy Krieger Institute, Johns Hopkins University School of Medicine (N.B.); Investigational Drug Service, Department of Pharmacy (M.H.), Johns Hopkins Hospital; and Johns Hopkins Bloomberg School of Public Health (A.S., G.Y.), Johns Hopkins Biostatistics Center, Baltimore, MD.
Joshua B EwenFrom the Departments of Neurology (C.L.S.-H., S.G., J.B.E., M.V.J., S.N.), Psychological and Brain Science (J.B.E.), Pediatrics (L.K., R.K.), Psychiatry (E.T.), and Psychology (R.V.), and the Neurogenetics Department (G.B.), Kennedy Krieger Institute, Johns Hopkins University School of Medicine (N.B.); Investigational Drug Service, Department of Pharmacy (M.H.), Johns Hopkins Hospital; and Johns Hopkins Bloomberg School of Public Health (A.S., G.Y.), Johns Hopkins Biostatistics Center, Baltimore, MD.
Manisha HongFrom the Departments of Neurology (C.L.S.-H., S.G., J.B.E., M.V.J., S.N.), Psychological and Brain Science (J.B.E.), Pediatrics (L.K., R.K.), Psychiatry (E.T.), and Psychology (R.V.), and the Neurogenetics Department (G.B.), Kennedy Krieger Institute, Johns Hopkins University School of Medicine (N.B.); Investigational Drug Service, Department of Pharmacy (M.H.), Johns Hopkins Hospital; and Johns Hopkins Bloomberg School of Public Health (A.S., G.Y.), Johns Hopkins Biostatistics Center, Baltimore, MD.
Lisa KratzFrom the Departments of Neurology (C.L.S.-H., S.G., J.B.E., M.V.J., S.N.), Psychological and Brain Science (J.B.E.), Pediatrics (L.K., R.K.), Psychiatry (E.T.), and Psychology (R.V.), and the Neurogenetics Department (G.B.), Kennedy Krieger Institute, Johns Hopkins University School of Medicine (N.B.); Investigational Drug Service, Department of Pharmacy (M.H.), Johns Hopkins Hospital; and Johns Hopkins Bloomberg School of Public Health (A.S., G.Y.), Johns Hopkins Biostatistics Center, Baltimore, MD.
Richard KelleyFrom the Departments of Neurology (C.L.S.-H., S.G., J.B.E., M.V.J., S.N.), Psychological and Brain Science (J.B.E.), Pediatrics (L.K., R.K.), Psychiatry (E.T.), and Psychology (R.V.), and the Neurogenetics Department (G.B.), Kennedy Krieger Institute, Johns Hopkins University School of Medicine (N.B.); Investigational Drug Service, Department of Pharmacy (M.H.), Johns Hopkins Hospital; and Johns Hopkins Bloomberg School of Public Health (A.S., G.Y.), Johns Hopkins Biostatistics Center, Baltimore, MD.
Elaine TierneyFrom the Departments of Neurology (C.L.S.-H., S.G., J.B.E., M.V.J., S.N.), Psychological and Brain Science (J.B.E.), Pediatrics (L.K., R.K.), Psychiatry (E.T.), and Psychology (R.V.), and the Neurogenetics Department (G.B.), Kennedy Krieger Institute, Johns Hopkins University School of Medicine (N.B.); Investigational Drug Service, Department of Pharmacy (M.H.), Johns Hopkins Hospital; and Johns Hopkins Bloomberg School of Public Health (A.S., G.Y.), Johns Hopkins Biostatistics Center, Baltimore, MD.
Rebecca VaurioFrom the Departments of Neurology (C.L.S.-H., S.G., J.B.E., M.V.J., S.N.), Psychological and Brain Science (J.B.E.), Pediatrics (L.K., R.K.), Psychiatry (E.T.), and Psychology (R.V.), and the Neurogenetics Department (G.B.), Kennedy Krieger Institute, Johns Hopkins University School of Medicine (N.B.); Investigational Drug Service, Department of Pharmacy (M.H.), Johns Hopkins Hospital; and Johns Hopkins Bloomberg School of Public Health (A.S., G.Y.), Johns Hopkins Biostatistics Center, Baltimore, MD.
Genila BibatFrom the Departments of Neurology (C.L.S.-H., S.G., J.B.E., M.V.J., S.N.), Psychological and Brain Science (J.B.E.), Pediatrics (L.K., R.K.), Psychiatry (E.T.), and Psychology (R.V.), and the Neurogenetics Department (G.B.), Kennedy Krieger Institute, Johns Hopkins University School of Medicine (N.B.); Investigational Drug Service, Department of Pharmacy (M.H.), Johns Hopkins Hospital; and Johns Hopkins Bloomberg School of Public Health (A.S., G.Y.), Johns Hopkins Biostatistics Center, Baltimore, MD.
Abanti SanyalFrom the Departments of Neurology (C.L.S.-H., S.G., J.B.E., M.V.J., S.N.), Psychological and Brain Science (J.B.E.), Pediatrics (L.K., R.K.), Psychiatry (E.T.), and Psychology (R.V.), and the Neurogenetics Department (G.B.), Kennedy Krieger Institute, Johns Hopkins University School of Medicine (N.B.); Investigational Drug Service, Department of Pharmacy (M.H.), Johns Hopkins Hospital; and Johns Hopkins Bloomberg School of Public Health (A.S., G.Y.), Johns Hopkins Biostatistics Center, Baltimore, MD.
Gayane YenokyanFrom the Departments of Neurology (C.L.S.-H., S.G., J.B.E., M.V.J., S.N.), Psychological and Brain Science (J.B.E.), Pediatrics (L.K., R.K.), Psychiatry (E.T.), and Psychology (R.V.), and the Neurogenetics Department (G.B.), Kennedy Krieger Institute, Johns Hopkins University School of Medicine (N.B.); Investigational Drug Service, Department of Pharmacy (M.H.), Johns Hopkins Hospital; and Johns Hopkins Bloomberg School of Public Health (A.S., G.Y.), Johns Hopkins Biostatistics Center, Baltimore, MD.
Nga BreretonFrom the Departments of Neurology (C.L.S.-H., S.G., J.B.E., M.V.J., S.N.), Psychological and Brain Science (J.B.E.), Pediatrics (L.K., R.K.), Psychiatry (E.T.), and Psychology (R.V.), and the Neurogenetics Department (G.B.), Kennedy Krieger Institute, Johns Hopkins University School of Medicine (N.B.); Investigational Drug Service, Department of Pharmacy (M.H.), Johns Hopkins Hospital; and Johns Hopkins Bloomberg School of Public Health (A.S., G.Y.), Johns Hopkins Biostatistics Center, Baltimore, MD.
Michael V JohnstonFrom the Departments of Neurology (C.L.S.-H., S.G., J.B.E., M.V.J., S.N.), Psychological and Brain Science (J.B.E.), Pediatrics (L.K., R.K.), Psychiatry (E.T.), and Psychology (R.V.), and the Neurogenetics Department (G.B.), Kennedy Krieger Institute, Johns Hopkins University School of Medicine (N.B.); Investigational Drug Service, Department of Pharmacy (M.H.), Johns Hopkins Hospital; and Johns Hopkins Bloomberg School of Public Health (A.S., G.Y.), Johns Hopkins Biostatistics Center, Baltimore, MD.
Sakkubai NaiduFrom the Departments of Neurology (C.L.S.-H., S.G., J.B.E., M.V.J., S.N.), Psychological and Brain Science (J.B.E.), Pediatrics (L.K., R.K.), Psychiatry (E.T.), and Psychology (R.V.), and the Neurogenetics Department (G.B.), Kennedy Krieger Institute, Johns Hopkins University School of Medicine (N.B.); Investigational Drug Service, Department of Pharmacy (M.H.), Johns Hopkins Hospital; and Johns Hopkins Bloomberg School of Public Health (A.S., G.Y.), Johns Hopkins Biostatistics Center, Baltimore, MD. Naidu@kennedykrieger.org.
Johns Hopkins Hospital · US

Funding

Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1M
NCATS NIH HHS UL1 TR001079
6 · The paper itself

Abstract

objectiveTo determine safety and perform a preliminary assessment of dose-dependent efficacy of dextromethorphan in normalizing electrographic spikes, clinical seizures, and behavioral and cognitive functions in girls with Rett syndrome.

methodsWe used a prospective randomized, open-label trial in fast metabolizers of dextromethorphan to examine the effect of dextromethorphan on core clinical features of Rett syndrome. Interictal spike activity and clinical seizures were determined using EEG and parent reporting. Cognitive data were obtained using the Mullen Scales of Early Learning and Vineland Adaptive Behavior Scales, while behavioral data were obtained from parent-completed checklists, the Aberrant Behavior Checklist-Community Version, and the Screen for Social Interaction. Anthropometric data were obtained according to the National Health and Nutrition Examination Survey. The Rett Syndrome Severity Scale provided a clinical global impression of the effect of dextromethorphan on clinical severity.

resultsDextromethorphan is safe for use in 3- to 15-year-old girls with Rett syndrome. Thirty-five girls were treated with 1 of 3 doses of dextromethorphan over a period of 6 months. Statistically significant dose-dependent improvements were seen in clinical seizures, receptive language, and behavioral hyperactivity. There was no significant improvement in global clinical severity as measured by the Rett Syndrome Severity Scale.

conclusionsDextromethorphan is a potent noncompetitive antagonist of the NMDA receptor channel that is safe for use in young girls with Rett syndrome. Preliminary evidence suggests that dextromethorphan may improve some core features of Rett syndrome. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that dextromethorphan at various doses does not change EEG spike counts over 6 months, though precision was limited to exclude an important effect.

Indexed as

AdolescentAnthropometryChildChild, PreschoolDextromethorphanElectroencephalographyExcitatory Amino Acid AntagonistsFemaleFollow-Up StudiesGaitHumansNeuropsychological TestsParentsRett SyndromeSeverity of Illness IndexStatistics, NonparametricDextromethorphanExcitatory Amino Acid Antagonists

Identifiers

PMID28931647
PMCPMC5644464
OpenAlexW2754980868

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.