Trial reportNature medicine2021
Inhibition of phosphodiesterase-4D in adults with fragile X syndrome: a randomized, placebo-controlled, phase 2 clinical trial.
Trial report in Nature medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 79 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 Randomized, Double-blind, Placebo-controlled, 2-period Crossover Study of BPN14770 in Adult Males With Fragile X Syndrome
Open-Label Trial of Sulforaphane in Premutation Carriers With FXTAS to Find Biomarkers
Evaluation of the Safety, Tolerability, and Effectiveness of CTH120 in Adult Males With Fragile X Syndrome
Who cites it
79 citing papers in PubMed, 2 syntheses or guidelines pooled it, 127 citations in OpenAlex.
- Pooled it
- Parent-reported outcome measures evaluating communication in individuals with rare neurodevelopmental disorders: A systematic review.International journal of language & communication disordersPooled it
- The effects of the PDE4 inhibitor roflumilast on cognitive performance after a cerebrovascular accident: a double-blind randomized placebo-controlled trial with an open label extension (ROSTMEMA).Journal of psychopharmacology (Oxford, England) · 2026Trial
- SPG601-associated modulation of resting-state EEG and improvement in executive function in a fragile X syndrome randomized controlled crossover study.Scientific reports · 2026Trial
- ROC Analysis of Biomarker Combinations in Fragile X Syndrome-Specific Clinical Trials: Evaluating Treatment Efficacy via Exploratory Biomarkers.Translational psychiatry · 2025Trial
- Towards precision psychiatry: initial foundations and future directions.Nature reviews. Drug discovery · 2026Review
- PDE4D-CXCL13 axis in gland epithelial cells promotes B cell infiltration in primary Sjögren's syndrome.Acta pharmacologica Sinica · 2026Article
- Clinical Trial Designs for Rare Disorders: A Scoping Review of the Effectiveness of Pharmacologic Interventions in Fragile X Syndrome.Neurology. Genetics · 2026Review
- Blarcamesine improves EEG biomarkers of cortical dysfunction in a mouse model of fragile X syndrome.Frontiers in pharmacology · 2026Article
- Clinical Relevance of NIH Toolbox Cognition Battery Developmental Change in Intellectual and Developmental Disabilities: Associations with Verbal Reasoning.American journal on intellectual and developmental disabilities · 2026Article
- Parallel paths: A narrative review exploring autism and its co-occurring conditions.World journal of clinical pediatrics · 2025Review
- The Emerging Role of Phosphodiesterase Inhibitors in Fragile X Syndrome and Autism Spectrum Disorder.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Differential effects of Phosphodiesterase 4A5 on cAMP-dependent forms of long-term potentiation.The Journal of physiology · 2025Article
- Multimodal analyses reveal genes driving electrophysiological maturation of neurons in the primate prefrontal cortex.Neuron · 2025Article
- Limitations of genomics to predict and treat autism: a disorder born in the womb.Journal of medical genetics · 2025Review
- Inhibition of the upregulated phosphodiesterase 4D isoforms improves SERCA2a function in diabetic cardiomyopathy.British journal of pharmacology · 2025Article
- From Discovery to Innovative Translational Approaches in 80 Years of Fragile X Syndrome Research.Biomedicines · 2025Review
- Therapeutic Effects of Pharmacological Modulation of Serotonin Brain System in Human Patients and Animal Models of Fragile X Syndrome.International journal of molecular sciences · 2025Review
- How close are we to a cAMP- and cGMP-theory-based pharmacological therapy for fragile X syndrome?Cell reports. Medicine · 2025Article
- Inhibition of GRK2-PDE4D Axis Suppresses Fibroblast-Like Synoviocytes Hyperplasia and Alleviates Experimental Arthritis.International journal of biological sciences · 2025Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
The goal of this study was to determine whether a phosphodiesterase-4D (PDE4D) allosteric inhibitor (BPN14770) would improve cognitive function and behavioral outcomes in patients with fragile X syndrome (FXS). This phase 2 trial was a 24-week randomized, placebo-controlled, two-way crossover study in 30 adult male patients (age 18-41 years) with FXS. Participants received oral doses of BPN14770 25 mg twice daily or placebo. Primary outcomes were prespecified as safety and tolerability with secondary efficacy outcomes of cognitive performance, caregiver rating scales and physician rating scales (ClinicalTrials.gov identifier: NCT03569631 ). The study met the primary outcome measure since BPN14770 was well tolerated with no meaningful differences between the active and placebo treatment arms. The study also met key secondary efficacy measures of cognition and daily function. Cognitive benefit was demonstrated using the National Institutes of Health Toolbox Cognition Battery assessments of Oral Reading Recognition (least squares mean difference +2.81, P = 0.0157), Picture Vocabulary (+5.81, P = 0.0342) and Cognition Crystallized Composite score (+5.31, P = 0.0018). Benefit as assessed by visual analog caregiver rating scales was judged to be clinically meaningful for language (+14.04, P = 0.0051) and daily functioning (+14.53, P = 0.0017). Results from this study using direct, computer-based assessment of cognitive performance by adult males with FXS indicate significant cognitive improvement in domains related to language with corresponding improvement in caregiver scales rating language and daily functioning.
Indexed as
Identifiers
What Socratic 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 Socratic graph.