Trial reportNature medicine2025
Pridopidine in early-stage manifest Huntington's disease: a phase 3 trial.
Trial report in Nature medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04556656 (A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel Arm, Multicenter Study Evaluating the Efficacy and Safety of Pridopidine in Patients With Early Stage of Huntington Disease), which is not on this map. Cited by 11 papers, 1 of them a synthesis 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 Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel Arm, Multicenter Study Evaluating the Efficacy and Safety of Pridopidine in Patients With Early Stage of Huntington Disease
Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Systematic Review of the Huntington's Disease Drug Development Pipeline, 2014 to 2025.Movement disorders : official journal of the Movement Disorder Society · 2026Pooled it
- Effects of time-restricted eating in early-stage Huntington's disease: a pilot study.Nature metabolism · 2026Article
- Translational Paradox of Triplet Repeat Expansion Disorders: Synthesizing Clinical Trial Failures to Guide Future Therapeutics.Clinical pharmacology and therapeutics · 2026Review
- Digital Motor Outcomes Capture Upper Limb and Mild Stage Impairment in Hereditary Spastic Paraplegia.Neurology and therapy · 2026Article
- Recommendations for the use of clinical outcome assessments in rare disease drug development.EClinicalMedicine · 2026Review
- Pridopidine Mediated Sigma-1 Receptor Activation and Therapeutic Implications in Neurodegenerative Diseases.Neurology international · 2026Review
- From glycemic control to neuroprotection: alogliptin as a repurposed candidate for Huntington's disease.Metabolic brain disease · 2026Review
- Sigma-1R-CD36 axis in myeloid cells contributes to the alleviation of depression-like behaviors.Journal of translational medicine · 2026Article
- A machine learning-derived speech index as a biomarker for Huntington's disease severity.Journal of neurology · 2026Article
- Pridopidine Protects ALS Patient-Derived Neural Progenitor Cells via Sigma-1 Receptor Activation.International journal of molecular sciences · 2026Article
- Pridopidine, a Potent and Selective Therapeutic Sigma-1 Receptor (S1R) Agonist for Treating Neurodegenerative Diseases.Pharmaceuticals (Basel, Switzerland) · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Huntington's disease (HD) is a rare, neurodegenerative disorder for which only symptomatic treatments are available. The PROOF-HD study was a randomized, double-blind, placebo-controlled phase 3 trial evaluating the efficacy and safety of pridopidine, a selective Sigma-1 receptor agonist, in HD. The primary and key secondary endpoints, change in total functional capacity (TFC) and composite Unified Huntington's Disease Rating Scale (cUHDRS) score at week 65, were not met in the overall population. The TFC least-squares mean difference between pridopidine and placebo was -0.18 (95% confidence interval -0.49 to 0.14; P = 0.26). The cUHDRS least-squares mean difference between pridopidine and placebo was -0.11 (95% confidence interval -0.40 to 0.18; P = 0.45). Sensitivity analysis in a subgroup of participants not treated with antidopaminergic medications at any time demonstrated a consistent pattern favoring pridopidine across multiple measures, including TFC and cUHDRS. Notably, pridopidine 45 mg twice daily demonstrated a favorable safety and tolerability profile. Taken together, pridopidine has the potential to address a critical unmet need in HD. ClinicalTrials.gov identifier: NCT04556656 .
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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.