Narcolepsy
diseaseOn this page
Also known as narcolepsy with or without cataplexynarcolepsy, without cataplexyparoxysmal sleep
Summary
Narcolepsy (MONDO:0021107) is a disease with 6 GWAS associations across 4 studies and 102 clinical trials. Top therapeutic interventions include pitolisant, modafinil, and armodafinil. A subtype of sleep-wake disorder — broader associated-gene and molecular evidence is on the parent page (see Disease family below).
At a glance
- GWAS associations: 6
- Clinical trials: 102
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | narcolepsy |
| Mondo ID | MONDO:0021107 |
| MeSH | D009290 |
| Orphanet | 619284 |
| DOID | DOID:8986 |
| ICD-10-CM | G47.41 |
| ICD-11 | 1201727099 |
| NCIT | C84489 |
| SNOMED CT | 60380001 |
| UMLS | C0027404 |
| MedGen | 45001 |
| GARD | 0022460 |
| Is cancer (heuristic) | no |
Also known as: narcolepsy with or without cataplexy · narcolepsy, without cataplexy · paroxysmal sleep
Data availability: 6 GWAS associations (4 studies).
Disease family
This is a subtype of sleep-wake disorder. Genetic, therapeutic, and trial evidence is largely curated at the broader-term level — see the parent page for the associated-gene cohort and molecular evidence.
Classification path: disease › human disease › disease by developmental or physiological process › sleep disorder › sleep-wake disorder › narcolepsy
Related subtypes (11): bruxism, recurrent hypersomnia, sleep apnea syndrome, hypersomnia, periodic limb movement disorder, REM sleep behavior disorder, autosomal dominant cerebellar ataxia, deafness and narcolepsy, hereditary sensory neuropathy-deafness-dementia syndrome, autoimmune encephalopathy with parasomnia and obstructive sleep apnea, circadian rhythm sleep disorder, sleep disorder, initiating and maintaining sleep
Subtypes (3): narcolepsy-cataplexy syndrome, narcolepsy without cataplexy, hereditary narcolepsy
Genetics & variants
GWAS landscape
6 GWAS associations across 4 studies. Top hits map to 3 distinct genes (as reported by GWAS).
Top associations by p-value
| rsID | p-value | Gene | Risk allele | Odds ratio |
|---|---|---|---|---|
| rs9271687 | 6e-18 | HLA-DRB1 - HLA-DQA1 | A | 0.45 |
| rs185284877 | 4e-14 | MUC13 | A | 3.04 |
| rs558773955 | 7e-13 | DSCAM | G | 3.4 |
| rs190772533 | 4e-12 | HSPA4 - RPL6P15 | A | 2.69 |
| rs148340742 | 5e-12 | THEMIS - PTPRK | A | 2.86 |
| rs576404797 | 4e-11 | LPIN3 | G | 3.81 |
Top studies (by case count)
| Study | Lead author | Year | Cases | Controls | Title |
|---|---|---|---|---|---|
| GCST90477562 | Verma A | 2024 | 1,079 | 449,612 | Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. |
| GCST90480022 | Verma A | 2024 | 414 | 121,317 | Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. |
| GCST90481880 | Verma A | 2024 | 414 | 121,317 | Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. |
| GCST007779 | Hallberg P | 2019 | 41 | 4,891 | Pandemrix-induced narcolepsy is associated with genes related to immunity and neuronal survival. |
Variant details and genetic-evidence tiers
Tier distribution (top 50 variants)
| Tier | Variants |
|---|---|
| Tier 1: coding | 0 |
| Tier 2: splice/UTR | 1 |
| Tier 3: regulatory | 0 |
| Tier 4: intronic/intergenic | 5 |
MAF distribution
| Bucket | Variants |
|---|---|
| common (>=0.05) | 1 |
| low_freq (0.01-0.05) | 0 |
| rare (<0.01) | 5 |
| unknown | 0 |
Functional consequences
| Consequence | Count |
|---|---|
| intergenic_variant | 4 |
| intron_variant | 1 |
| 3_prime_UTR_variant | 1 |
Top variants
| rsID | Chr | Pos | Alleles | MAF | Consequence | Gene | p-value | Tier |
|---|---|---|---|---|---|---|---|---|
| rs9271687 | 6 | 32625208 | A>G,T | 0.162 | intergenic_variant | HLA-DRB1 - HLA-DQA1 | 6e-18 | Tier 4: intronic/intergenic |
| rs185284877 | 3 | 124943465 | A>C | 0.001 | intergenic_variant | MUC13 | 4e-14 | Tier 4: intronic/intergenic |
| rs558773955 | 21 | 40665321 | G>A,C | 0.001 | intron_variant | DSCAM | 7e-13 | Tier 4: intronic/intergenic |
| rs190772533 | 5 | 133143182 | A>G | 0.001 | intergenic_variant | HSPA4 - RPL6P15 | 4e-12 | Tier 4: intronic/intergenic |
| rs148340742 | 6 | 127942572 | A>G | 0.001 | intergenic_variant | THEMIS - PTPRK | 5e-12 | Tier 4: intronic/intergenic |
| rs576404797 | 20 | 41359205 | G>A | 0 | 3_prime_UTR_variant | LPIN3 | 4e-11 | Tier 2: splice/UTR |
Genes & proteins
No associated-gene cohort resolved for this disease. Atlas builds the molecular and therapeutic sections — associated genes, protein families, druggability, pathways, interactions, and drug associations — by aggregating over a disease’s associated genes (resolved via GWAS / GenCC / ClinVar / CIViC), and none resolved here. This is expected for antibody-mediated, autoimmune, or otherwise non-gene-defined conditions; the curated evidence for this disease is its clinical features, GWAS susceptibility, and clinical trials (above).
Function
No pathway enrichment — requires an associated-gene cohort.
Therapeutics
Drugs indicated for this disease
4 approved, 2 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.
| Drug | Development status |
|---|---|
| Armodafinil | Approved (phase 4) |
| Dextroamphetamine | Approved (phase 4) |
| Methylphenidate | Approved (phase 4) |
| Modafinil | Approved (phase 4) |
| Pitolisant | Phase 3 (in late-stage trials) |
| Solriamfetol | Phase 3 (in late-stage trials) |
Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Clarithromycin, Mazindol.
Clinical trials & evidence
Clinical trials
Clinical trials: 102.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 49 |
| PHASE3 | 21 |
| PHASE2 | 14 |
| PHASE1 | 13 |
| PHASE4 | 3 |
| PHASE1/PHASE2 | 1 |
| EARLY_PHASE1 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT04794491 | PHASE4 | COMPLETED | An Interventional Safety Switch Study (Segue Study) of XYWAV in Narcolepsy |
| NCT05869773 | PHASE4 | COMPLETED | A Switch Study From High-Sodium Oxybate to Xywav to Evaluate Changes in Blood Pressure in Participants With Narcolepsy |
| NCT05875974 | PHASE4 | COMPLETED | A Study to Investigate the Effect of XYWAV on Sleepiness, Polysomnography, and Functional Outcomes in Participants With Idiopathic Hypersomnia or Narcolepsy |
| NCT07540364 | PHASE3 | NOT_YET_RECRUITING | A Phase 3 Study to Evaluate the Efficacy and Safety of Samelisant in Patients With Narcolepsy |
| NCT00049803 | PHASE3 | COMPLETED | Safety and Efficacy of Xyrem Oral Solution (Sodium Oxybate) Compared With Placebo in Narcoleptic Patients |
| NCT00066170 | PHASE3 | COMPLETED | Trial Comparing Effects of Xyrem Taken Orally and Modafinil With Placebo in Treating Daytime Sleepiness in Narcolepsy |
| NCT00078312 | PHASE3 | COMPLETED | Armodafinil (CEP-10953) for Treatment of Narcolepsy, Obstructive Sleep Apnea/Hypopnea Syndrome, or Chronic Shift Work Sleep Disorder |
| NCT00078377 | PHASE3 | COMPLETED | Safety and Efficacy Study of Armodafinil (CEP-10953) in the Treatment of Excessive Sleepiness Associated With Narcolepsy |
| NCT00107796 | PHASE3 | COMPLETED | Study of PROVIGIL ® (Modafinil) Treatment in Children and Adolescents With Excessive Sleepiness Associated With Narcolepsy |
| NCT00107848 | PHASE3 | COMPLETED | PROVIGIL® (Modafinil) Treatment in Children and Adolescents With Excessive Sleepiness Associated With Narcolepsy or Obstructive Sleep Apnea/Hypopnea Syndrome |
| NCT00132873 | PHASE3 | COMPLETED | Trial of Xyrem® (Sodium Oxybate) for the Treatment of Narcolepsy |
| NCT00214968 | PHASE3 | COMPLETED | Assess the Safety and Effectiveness of PROVIGIL Treatment in Children and Adolescents With Excessive Sleepiness |
| NCT00228553 | PHASE3 | COMPLETED | Extension Study of the Safety and Efficacy of Armodafinil in the Treatment of Patients With Excessive Sleepiness |
| NCT00228566 | PHASE3 | COMPLETED | Study to Assess Patient Reported Outcomes With Armodafinil Treatment for Excessive Sleepiness in Adults With Narcolepsy or Obstructive Sleep Apnea/Hypopnea Syndrome |
| NCT01067222 | PHASE3 | COMPLETED | Efficacy and Safety Study of BF2.649 in the Treatment of Excessive Daytime Sleepiness in Narcolepsy |
| NCT01067235 | PHASE3 | COMPLETED | Efficacy and Safety Study of BF2.649 and BF2.649 Add on Modafinil on Cataplexy in Patients With Narcolespy |
| NCT01399606 | PHASE3 | COMPLETED | Long Term Open Label Study in Narcolepsy With BF2.649 (Pitolisant) |
| NCT01789398 | PHASE3 | COMPLETED | Patient Narcoleptic Treated With BF2.649 (Pitolisant) in add-on to Sodium Oxybate (HARMONY IV) |
| NCT02348593 | PHASE3 | COMPLETED | Twelve-week Study of the Safety and Efficacy of JZP-110 in the Treatment of Excessive Sleepiness in Narcolepsy |
| NCT02348632 | PHASE3 | COMPLETED | A Long-Term Safety Study of JZP-110 in the Treatment of Excessive Sleepiness in Subjects With Narcolepsy or OSA |
| NCT02720744 | PHASE3 | COMPLETED | Once-Nightly Sodium Oxybate for Treatment of Excessive Daytime Sleepiness and Cataplexy in Narcolepsy |
| NCT04451668 | PHASE3 | COMPLETED | An Open Label Study of FT218 in Subjects With Narcolepsy |
| NCT05059223 | PHASE3 | COMPLETED | A Study to Assess the Efficacy and Safety of AXS-12 (Reboxetine) in Patients With Narcolepsy |
| NCT05113745 | PHASE3 | COMPLETED | A Study to Assess the Long-term Efficacy and Safety of AXS-12 (Reboxetine) in Subjects With Narcolepsy (ENCORE) |
| NCT07493265 | PHASE2 | RECRUITING | A Study to Evaluate the Efficacy and Safety of E2086 in Adults With Narcolepsy |
| NCT00366080 | PHASE2 | TERMINATED | Effectiveness Of The Drug GSK189254 In Treating Patients With Narcolepsy |
| NCT00424931 | PHASE2 | COMPLETED | A Safety and Effectiveness Study of a Single Dose of JNJ-17216498 in Patients With Narcolepsy |
| NCT01006122 | PHASE2 | COMPLETED | A Study Of A Novel Compound For Excessive Daytime Sleepiness Associated With Narcolepsy |
| NCT01146600 | PHASE2 | COMPLETED | Clarithromycin for the Treatment of Hypersomnia |
| NCT01485770 | PHASE2 | COMPLETED | A Study of the Safety and Effectiveness of ADX-N05 in the Treatment of Excessive Daytime Sleepiness |
| NCT01681121 | PHASE2 | COMPLETED | A Study of the Safety and Effectiveness of ADX-N05 for Excessive Daytime Sleepiness in Subjects With Narcolepsy |
| NCT02806908 | PHASE2 | COMPLETED | Study Assessing Effects of JZP-110 on Driving Performance in the Treatment of Excessive Sleepiness in Narcolepsy |
| NCT02821715 | PHASE2 | COMPLETED | Safety and Efficacy of THN102 on Sleepiness in Narcoleptic Patients |
| NCT02832336 | PHASE1/PHASE2 | COMPLETED | The Effect of Caffeine on the Narcoleptic Patients |
| NCT03267303 | PHASE2 | COMPLETED | A Study to Evaluate the Safety and Efficacy of TS-091 in Patients with Narcolepsy |
| NCT03881852 | PHASE2 | COMPLETED | Clinical Outcomes in Narcolepsy and Cataplexy: An Evaluation of Reboxetine Treatment (CONCERT) |
| NCT04072380 | PHASE2 | COMPLETED | A Study to Evaluate Safety, and Efficacy of SUVN-G3031 (Samelisant) in Patients With Narcolepsy With and Without Cataplexy |
| NCT04923594 | PHASE2 | COMPLETED | Four-week Study of the Safety and Efficacy of NLS-2 (Mazindol Extended Release) in the Treatment of Narcolepsy |
| NCT05055024 | PHASE2 | COMPLETED | An Open Label Study of NLS-2 (Mazindol Extended Release) in Subjects With Narcolepsy |
| NCT07613710 | PHASE1 | RECRUITING | A Trial to Test the Safety and Tolerability of Lu AH69593 in Adults That Are Healthy or Have Narcolepsy |
Drugs tested across these trials (top 30)
| Molecule | Max phase | Trials referencing |
|---|---|---|
| PITOLISANT | 4 | 15 |
| MODAFINIL | 4 | 11 |
| ARMODAFINIL | 4 | 6 |
| OXYBATE | 4 | 5 |
| SOLRIAMFETOL | 4 | 4 |
| CAFFEINE | 4 | 1 |
| DEXTROAMPHETAMINE | 4 | 1 |
| MAZINDOL | 4 | 1 |
| SUVN-G3031 | 2 | 3 |
| DANAVOREXTON | 2 | 1 |
| GSK189254 | 2 | 1 |
| JNJ-17216498 | 2 | 1 |
| PF-03654746 | 2 | 1 |
Related Atlas pages
- Drugs: Pitolisant, Modafinil, Armodafinil, Oxybate, Solriamfetol, Caffeine, Dextroamphetamine, Mazindol