Trial reportJournal of neurodevelopmental disorders2022
A randomized, double-blind, placebo-controlled phase II trial to explore the effects of a GABA
Trial report in Journal of neurodevelopmental disorders, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02024789 (A MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 2 STUDY OF THE EFFICACY, SAFETY AND TOLERABILITY OF RG1662 IN ADULTS AND ADOLESCENTS WITH DOWN SYNDROME), which is not on this map. Cited by 30 papers, 2 of them syntheses that pooled 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.
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.
A multi-center, randomized, double-blind, placebo-controlled phase 2 study of the efficacy, safety and tolerability of rg1662 in adults and adolescents with down syndrome (clematis)
Who cites it
30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 42 citations in OpenAlex.
- The effect of exercise on improving cognitive function in people with Down's syndrome: a systematic review and meta-analysis.European journal of pediatrics · 2025Pooled it
- Assessing the effectiveness of measurement scales in evaluating the health-related quality of life in rare disease patients after treatment: a systematic review.Health and quality of life outcomes · 2024Pooled it
- Trial
- Excess EEG beta-band oscillations in Dup15q syndrome correlate with clinical severity.Translational psychiatry · 2026Article
- Systematic multi-omic deconvolution of the clinical heterogeneity of Down syndrome.Nature communications · 2026Article
- Targeting γ-aminobutyric acid type A receptors to mitigate perioperative neurocognitive disorders: a narrative review.British journal of anaesthesia · 2026Review
- Negative allosteric modulation of α5-GABAbioRxiv : the preprint server for biology · 2026Article
- Direct modulation of human GABA-A αFrontiers in neuroscience · 2026Review
- Role of cystathionine-β-synthase and hydrogen sulfide in down syndrome.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- The Role of GABA Pathway Components in Pathogenesis of Neurodevelopmental Disorders.International journal of molecular sciences · 2025Review
- Synaptic inhibitory dynamics drive benzodiazepine response in pediatric status epilepticus.Epilepsia · 2025Article
- Neuronal oscillations in cognition: Down syndrome as a model of mouse to human translation.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2025Review
- Current insights and prospects for the pathogenesis and treatment of clinical manifestations associated with Down syndrome through neurotransmitter, inflammatory, and oxidative stress pathways.Frontiers in pharmacology · 2025Review
- Inhibition of NMDA receptors and other ion channel types by membrane-associated drugs.Frontiers in pharmacology · 2025Review
- Exploring the Potential of Pyridine Carboxylic Acid Isomers to Discover New Enzyme Inhibitors.Drug design, development and therapy · 2025Review
- A Review of Clinical Trials in Down Syndrome.International review of research in developmental disabilities · 2025Article
- Drug Treatments for Neurodevelopmental Disorders: Targeting Signaling Pathways and Homeostasis.Current neurology and neuroscience reports · 2024Review
- Consequences of trisomy 21 for brain development in Down syndrome.Nature reviews. Neuroscience · 2024Review
- Haploinsufficiency of GABAThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Basmisanil, an α5-GABANeuroscience letters · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThere are currently no pharmacological therapies to address the intellectual disability associated with Down syndrome. Excitatory/inhibitory imbalance has been hypothesized to contribute to impairments in cognitive functioning in Down syndrome. Negative modulation of the GABA
methodsBasmisanil, a selective GABA
resultsBasmisanil was safe and well-tolerated; the frequency and nature of adverse events were similar in basmisanil and placebo arms. EEG revealed treatment-related changes in spectral power (increase in low ~ 4-Hz and decrease in high ~ 20-Hz frequencies) providing evidence of functional target engagement. All treatment arms had a similar proportion of participants showing above-threshold improvement on the primary composite endpoint, evaluating concomitant responses in cognition and independent functioning (29% in placebo, 20% in low dose, and 25% in high dose). Further analysis of the individual measures contributing to the primary endpoint revealed no difference between placebo and basmisanil-treated groups in either adolescents or adults. There were also no differences across the secondary endpoints assessing changes in executive function, language, or quality of life.
conclusionsBasmisanil did not meet the primary efficacy objective of concomitant improvement on cognition and adaptive functioning after 6 months of treatment, despite evidence for target engagement. This study provides key learnings for future clinical trials in Down syndrome.
trial registrationThe study was registered on December 31, 2013, at clinicaltrials.gov as NCT02024789.
Indexed as
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What OpenQuestion holds
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.