Evidence map›Paper›PMID 34490850›Full record

Trial reportPain2022

Randomized, double-blind, placebo-controlled trial of ISC 17536, an oral inhibitor of transient receptor potential ankyrin 1, in patients with painful diabetic peripheral neuropathy: impact of preserved small nerve fiber function.

Sunil M Jain, Ramanathan Balamurugan, Monika Tandon, Neelufar Mozaffarian, Girish Gudi, Yacine Salhi, Robert Holland, Roy Freeman, Ralf Baron

Open access · hybridAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Pain, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
4.6field-weighted citation impact, top 4% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

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

  1. Pooled it
  2. Article
  3. Innovative Diabetes Therapies and Impact on Peripheral and Autonomic Diabetic Neuropathies: A State-of-the-Art Review.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2026
    Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. Review
  10. Diabetic neuropathy: cutting-edge research and future directions.Signal transduction and targeted therapy · 2025
    Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. 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

9 authors at 7 institutions in 3 countries.

Sunil M JainTOTALL Diabetes Hormone Institute, Indore, India.
Ramanathan BalamuruganKovai Diabetes Speciality Centre and Hospital, Coimbatore, India.
Monika TandonClinical Sciences, Glenmark Pharmaceuticals Limited, Mumbai, India.
Neelufar MozaffarianJanssen Pharmaceuticals, Inc, Cambridge, MA, United States.ORCID 0000-0002-5252-8363
Girish GudiIchnos Sciences, Inc, New York, NY, United States.
Yacine SalhiIchnos Sciences, Inc, New York, NY, United States.
Robert HollandEarly Clinical Development Consulting Ltd, Macclesfield, United Kingdom.ORCID 0000-0002-1316-2151
Roy FreemanDepartment of Neurology, Harvard Medical School, Boston, MA, United States.ORCID 0000-0003-3976-6022
Ralf BaronDivision of Neurological Pain Research and Therapy, Universitätsklinikum Schleswig-Holstein, Campus-Kiel, Germany.
Ichnos Sciences (United States) · USGlenmark Pharmaceuticals (India) · INHarvard University · USJanssen (United States) · USKovai Medical Center and Hospital · INTOTALL Diabetes Hormone Institute · INUniversity Hospital Schleswig-Holstein · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

abstractPatients with chronic pain syndromes, such as those with painful peripheral neuropathy due to diabetes mellitus, have limited treatment options and suffer ongoing attrition of their quality of life. Safer and more effective treatment options are needed. One therapeutic approach encompasses phenotypic characterization of the neuropathic pain subtype, combined with the selection of agents that act on relevant mechanisms. ISC 17536 is a novel, orally available inhibitor of the widely expressed pain receptor, transient receptor potential ankyrin 1, which mediates nociceptive signaling in peripheral small nerve fibers. In this randomized, placebo-controlled, proof-of-concept trial, we assessed the safety and efficacy of 28-day administration of ISC 17536 in 138 patients with chronic, painful diabetic peripheral neuropathy and used quantitative sensory testing to characterize the baseline phenotype of patients. The primary end point was the change from baseline to end of treatment in the mean 24-hour average pain intensity score based on an 11-point pain intensity numeric rating scale. The study did not meet the primary end point in the overall patient population. However, statistically significant and clinically meaningful improvement in pain were seen with ISC 17536 in an exploratory hypothesis-generating subpopulation of patients with preserved small nerve fiber function defined by quantitative sensory testing. These results may provide a mechanistic basis for targeted therapy in specific pain phenotypes in line with current approaches of "precision medicine" or personalized pain therapeutics. The hypothesis is planned to be tested in a larger phase 2 study.

Indexed as

Chronic PainDiabetes MellitusDiabetic NeuropathiesNeuralgiaAnkyrinsDouble-Blind MethodHumansNerve FibersPainPeripheral Nervous System DiseasesQuality of LifeTreatment OutcomeAnkyrins

Identifiers

PMID34490850
PMCPMC9100440
OpenAlexW3198913332

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.