Evidence map›Paper›PMID 28453471›Full record

Trial reportJournal of Alzheimer's disease : JAD2017

A Randomized, Double-Blind, Placebo-Controlled, Phase II Study of Oral ELND005 (scyllo-Inositol) in Young Adults with Down Syndrome without Dementia.

Michael S Rafii, Brian G Skotko, Mary Ellen McDonough, Margaret Pulsifer, Casey Evans, Eric Doran, Gabriela Muranevici, Patrick Kesslak, Susan Abushakra, Ira T Lott and 1 more

Registry-linked trialOpen access · greenAbstract readClinical Trial, Phase IIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of Alzheimer's disease : JAD, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01791725 (A 4-Week Randomized, Double-Blind, Placebo-Controlled, Phase 2a Safety and PK Study of Oral ELND005 in Young Adults With Down Syndrome Without Dementia), which is not on this map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 10% 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.

NCT01791725 phase2completednot on this map

A 4-Week Randomized, Double-Blind, Placebo-Controlled, Phase 2a Safety and PK Study of Oral ELND005 in Young Adults With Down Syndrome Without Dementia

TypeinterventionalSponsorOPKO Health, Inc.Ran2013 to 2014Enrolled23ConditionsDown SyndromeArmsELND005, Placebo
3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.

  1. Pooled it
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  15. Diagnosis and Treatment of Alzheimer's Disease:: An Update.Delaware journal of public health · 2021
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  17. Review
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  19. Further understanding the connection between Alzheimer's disease and Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2020
    Review
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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

11 authors at 7 institutions in 1 country.

Michael S RafiiAlzheimer's Therapeutic Research Institute (ATRI) at University of Southern California, San Diego, CA, USA.
Brian G SkotkoDepartment of Pediatrics, Down Syndrome Program, Division of Medical Genetics, Massachusetts General Hospital, Boston, MA, USA.
Mary Ellen McDonoughDepartment of Pediatrics, Down Syndrome Program, Division of Medical Genetics, Massachusetts General Hospital, Boston, MA, USA.
Margaret PulsiferHarvard Medical School, Boston, MA, USA.
Casey EvansDepartment of Psychiatry, Psychology Assessment Center, Massachusetts General Hospital, Boston, MA, USA.
Eric DoranDepartment of Pediatrics, University of California, Irvine, CA, USA.
Gabriela MuraneviciDepartment of Neurosciences, University of California, San Diego, CA, USA.
Patrick KesslakACADIA Pharmaceuticals, San Diego, CA, USA.
Susan AbushakraAlzheon, Inc., Framingham, MA, USA.
Ira T LottDepartment of Pediatrics, University of California, Irvine, CA, USA.
ELND005-DS Study Group
Massachusetts General Hospital · USUniversity of California, Irvine · USAcadia Pharmaceuticals (United States) · USAutism Research Institute · USFramingham State University · USHarvard University · USUniversity of California, San Diego · US

Funding

UC Irvine Alzheimer's Disease Research Center Induced Pluripotent Stem Cell CoreP50AG016573 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI LAFERLA, FRANK M · 2000 to 2019
$37.0M
University of California Health Participation in the National COVID Cohort Collaborative (N3C)UL1TR001414 · NCATS · UNIVERSITY OF CALIFORNIA-IRVINE · PI COOPER, DAN M, VILAIN, ERIC J. · 2015 to 2023
$35.1M
Institute for Clinical and Translational ScienceUL1TR000153 · NCATS · UNIVERSITY OF CALIFORNIA-IRVINE · PI COOPER, DAN M · 2012 to 2015
$12.1M
NCATS NIH HHS UL1 TR000153NCATS NIH HHS UL1 TR001414NIA NIH HHS P50 AG016573
6 · The paper itself

Abstract

backgroundELND005 (scyllo-Inositol; cyclohexane-1,2,3,4,5,6-hexol) has been evaluated as a potential disease-modifying treatment for Alzheimer's disease (AD). Individuals with Down syndrome (DS) have an increased risk for developing AD dementia.

objectiveTo evaluate the safety and tolerability of ELND005 and to determine its pharmacokinetics (PK) and relationship between PK parameters, safety outcome measures, and exploratory efficacy outcome measures in young adults with DS without dementia.

methodsThis was a prospective, randomized, double-blind, placebo-controlled, parallel-group, three-arm, multicenter Phase II study of the safety and pharmacokinetics of ELND005 administered orally for 4 weeks (ClinicalTrials.gov NCT01791725). Participants who met study eligibility criteria were randomly assigned in a 2 : 1:1 ratio to receive ELND005 at either 250 mg twice daily (BID) or 250 mg once daily (QD) or matching placebo for 4 weeks.

resultsThere were no apparent treatment group-related trends on cognitive or behavioral measures and there were no SAEs and no deaths in the study. Overall, mean changes from baseline in clinical laboratory parameters, vital sign measurements, electrocardiogram results, and other physical findings were unremarkable. ELND005 accumulation averaged approximately 2-fold with QD dosing, and 3- to 4-fold with BID dosing.

conclusionOverall, treatment of adults with DS with ELND005 at both doses was well tolerated, achieved measurable blood levels and demonstrated no safety findings. Further studies will be needed to test efficacy.

Indexed as

Administration, OralAdolescentAdultCognition DisordersDouble-Blind MethodDown SyndromeElectrocardiographyFemaleHumansInositolMagnetic Resonance ImagingMaleMental DisordersProspective StudiesPsychiatric Status Rating ScalesTreatment OutcomeInositolscyllitolAlzheimer’s diseaseamyloiddementiaDown syndromeMyo-inositol

Identifiers

PMID28453471
PMCPMC5777855
OpenAlexW2608559677

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

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.