Evidence map›Paper›PMID 28124585›Full record

Trial reportCurrent Alzheimer research2017

Poor Safety and Tolerability Hamper Reaching a Potentially Therapeutic Dose in the Use of Thalidomide for Alzheimer's Disease: Results from a Double-Blind, Placebo-Controlled Trial.

Boris Decourt, Denise Drumm-Gurnee, Jeffrey Wilson, Sandra Jacobson, Christine Belden, Sherye Sirrel, Michael Ahmadi, Holly Shill, Jessica Powell, Aaron Walker and 3 more

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

Trial report in Current Alzheimer research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06639282 (SIPO1-AD), which is not on this map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
5.7field-weighted citation impact, top 3% 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.

NCT06639282 phase2recruitingnot on this mapstarted 2025, after this paper: background citation

SIPO1-AD: A Phase II Clinical Trial for the Assessment of Safety, Tolerability, and Efficacy of Siponimod in Patients With Mild Alzheimer's Disease

TypeinterventionalSponsorSt. Joseph's Hospital and Medical Center, PhoenixRan2025 to 2029Enrolled105ConditionsAlzheimer Disease, Mild Alzheimer Disease, MCI With Increased Risk for Alzheimer Disease, Cognitive Impairment, MildArmsSiponimod, Placebo
3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.

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  12. Repurposing Pomalidomide as a Neuroprotective Drug: Efficacy in an Alpha-Synuclein-Based Model of Parkinson's Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022
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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

13 authors at 2 institutions in 1 country.

Boris Decourtthe Barrow Neurological Institute, 240 West Thomas, Suite 301, Phoenix, AZ 85013, United States.
Denise Drumm-GurneeBarrow Neurological Institute, 240 West Thomas, Suite 301, Phoenix, AZ 85013, United States.
Jeffrey WilsonDepartment of Mathematics, Arizona State University, Tempe AZ, United States.
Sandra JacobsonBarrow Neurological Institute, 240 West Thomas, Suite 301, Phoenix, AZ 85013, United States.
Christine BeldenBarrow Neurological Institute, 240 West Thomas, Suite 301, Phoenix, AZ 85013, United States.
Sherye SirrelBarrow Neurological Institute, 240 West Thomas, Suite 301, Phoenix, AZ 85013, United States.
Michael AhmadiBarrow Neurological Institute, 240 West Thomas, Suite 301, Phoenix, AZ 85013, United States.
Holly ShillBarrow Neurological Institute, 240 West Thomas, Suite 301, Phoenix, AZ 85013, United States.
Jessica PowellBarrow Neurological Institute, 240 West Thomas, Suite 301, Phoenix, AZ 85013, United States.
Aaron WalkerBarrow Neurological Institute, 240 West Thomas, Suite 301, Phoenix, AZ 85013, United States.
Amanda GonzalesBarrow Neurological Institute, 240 West Thomas, Suite 301, Phoenix, AZ 85013, United States.
Mimi MaciasBarrow Neurological Institute, 240 West Thomas, Suite 301, Phoenix, AZ 85013, United States.
Marwan N SabbaghBarrow Neurological Institute, 240 West Thomas, Suite 301, Phoenix, AZ 85013, United States.
Barrow Neurological Institute · USArizona State University · US

Funding

Research Education ComponentP30AG019610 · NIA · SUN HEALTH RESEARCH INSTITUTE · PI REIMAN, ERIC MICHAEL · 2001 to 2020
$32.5M
Study on Thalidomide as BACE1 inhibitor in Alzhiemer's diseaseR01AG034155 · NIA · BANNER SUN HEALTH RESEARCH INSTITUTE · PI SABBAGH, MARWAN NOEL · 2009 to 2010
$1.7M
Pre-clinical testing of lenalidomide as pleiotropic therapeutics of Alzheimer's diseaseK01AG047279 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI DECOURT, BORIS · 2015 to 2019
$534k
NIA NIH HHS K01 AG047279NIA NIH HHS P30 AG019610NIA NIH HHS R01 AG034155
6 · The paper itself

Abstract

introductionTo date there is no cure for Alzheimer's disease (AD). After amyloid beta immunotherapies have failed to meet primary endpoints of slowing cognitive decline in AD subjects, the inhibition of the beta-secretase BACE1 appears as a promising therapeutic approach. Pre-clinical data obtained in APP23 mice suggested that the anti-cancer drug thalidomide decreases brainBACE1 and Aβ levels. This prompted us to develop an NIH-supported Phase IIa clinical trial to test the potential of thalidomide for AD. We hypothesized that thalidomide can decrease or stabilize brain amyloid deposits, which would result in slower cognitive decline in drug- versus placebo-treated subjects.

methodsThis was a 24-week, randomized, double-blind, placebo-controlled, parallel group study with escalating dose regimen of thalidomide with a target dose of 400mg daily in patients with mild to moderate AD. The primary outcome measures were tolerability and cognitive performance assessed by a battery of tests.

resultsA total of 185 subjects have been pre-screened, out of which25 were randomized. Mean age of the sample at baseline was 73.64 (±7.20) years; mean education was 14.24 (±2.3) years; mean MMSE score was 21.00 (±5.32); and mean GDS score was 2.76 (±2.28).Among the 25 participants, 14 (56%) terminated early due to adverse events, dramatically decreasing the power of the study. In addition, those who completed the study (44%) never reached the estimated therapeutic dose of 400 mg/day thalidomide because of reported adverse events. The cognitive data showed no difference between the treated and placebo groups at the end of the trial.

conclusionThis study demonstrates AD patients have poor tolerability for thalidomide, and are unable to reach a therapeutic dose felt to be sufficient to have effects on BACE1. Because of poor tolerability, this study failed to demonstrate a beneficial effect on cognition.

Indexed as

AgedAged, 80 and overAlzheimer DiseaseCognitionDouble-Blind MethodEducational StatusFemaleHumansImmunosuppressive AgentsMaleMiddle AgedPatient DropoutsThalidomideTreatment FailureImmunosuppressive AgentsThalidomideAdverse eventsAlzheimer's Diseaseclinical trialcognitive teststhalidomidetolerability.

Identifiers

PMID28124585
PMCPMC5706445
OpenAlexW2585865211

What OpenQuestion holds

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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.