# Insomnia

[Home](../README.md) · [Sleep](../WATCHLIST.md#sleep-health) · [Calendar](../MILESTONES.md)

Tags: [Drugs and biologics](../BROWSE.md#drugs) · [Devices and procedures](../BROWSE.md#devices-procedures)

## Current state

eNightfall adds a randomized test of stepped digital CBT-I with remission and 12-month follow-up in cancer survivors. Existing onset/maintenance drug indications, clinical insomnia outcomes and laboratory sleep-architecture measurements remain separate.

Status: active. Topic ID: `sleep_insomnia`.

## Questions to follow

- Follow difficulty falling asleep, staying asleep and early-morning waking as overlapping symptom patterns; distinguish trial eligibility, approved indication and demonstrated benefit.
- Compare CBT-I, validated digital therapies and medicines through remission, daytime function, durability, adherence and safety, alongside sleep-study measurements.
- Follow measured REM/N3 duration and percentage, fragmentation and within-night timing when reported. More of a stage is not automatically clinical benefit; wearable estimates and EEG-based polysomnography are different evidence.
- Keep orexin antagonists for insomnia separate from orexin agonists for hypersomnolence. Cross-link mental-health-related sleep research rather than merging indications.

## Programs and next milestones

### Focused update — 2026-10-16

<span class="note-anchor" id="note-2026-10-15-enightfall-cbti-registration"></span>

#### eNightfall will compare stepped digital CBT-I with standard treatment

**eNightfall / NCT07876661, first posted October 15.** Vrije Universiteit Brussel plans a three-arm randomized study in **140 adult cancer survivors with insomnia in Belgium**, comparing guided stepped web-based CBT-I, a standard 10-week web-based CBT-I program, and usual care with a sleep-hygiene leaflet.

Stepped treatment begins with four weeks of lower-intensity coaching; persistent symptoms trigger six more weeks of fuller CBT-I. Primary measures are **ISI severity and protocol-defined remission** after treatment and at **6 and 12 months**. Fatigue, quality of life, healthcare use and productivity are secondary. This tests scalable access and sustained clinical outcomes, not sleep-stage proportions.

The protocol has a threshold inconsistency: the escalation description uses **ISI <11**, while the primary remission definition says **≤11**. Do not silently harmonize these cutoffs. Participants cannot be fully blinded to behavioral content despite the registry’s masking label.

Status remains **not yet recruiting** after an estimated **October 15 start**. Estimated primary completion is **January 1, 2030**, final **April 1, 2030**. No results or superiority claim; this does not establish a new U.S. cleared digital product.

**Sources:** [Source 1](https://clinicaltrials.gov/study/NCT07876661).

**Remaining gaps:** Read current canonical scope, shared summaries, state and assigned topic notes. Bounded registry discovery covered July 18–October 16, 2026; prior October 13 findings were deduplicated. Full-topic successful-check dates remain unchanged.; Retrieved all 291 records across 3 pages of the bounded ClinicalTrials.gov query, plus 6 named records. Selected relevant new/changed protocols were appraised; downloading all records does not establish exhaustive safety/results review.; Europe PMC original-literature discovery failed with HTTP 503 for this topic. Targeted primary-source web searches supplied a partial fallback. Worldwide literature, regulators, international registries and complete original conference/podcast recordings remain incomplete.; The new condition baseline remains incomplete. Preceding 90-day registry discovery and selected inherited pivotal context were checked; the full older clinical, label and behavioral/device evidence corpus has not been completed.; Selected eNightfall because it assesses clinical remission and follow-up rather than only laboratory physiology. Prior SMART, DARI-DREAM, COMISA-PEC and BELL-001 entries retained. Established medicine labeling, architecture endpoints and complete CBT-I/digital durability baseline remain incomplete.

**Informal-source coverage:** Targeted insomnia informal searches returned personal experiences and general prescribing discussions, without a distinct new formal development claim selected. TAK-360 nighttime-sleep account is recorded once under hypersomnolence. No rate or architecture effect inferred; full podcast/talk census incomplete.

[Full coverage record](../updates/2026-10-16_scheduled_research_update.md).


### Focused update — 2026-10-13

<span class="note-anchor" id="note-2026-10-13-bell001-registration"></span>

#### A breathing-linked sound application registers a sham-controlled laboratory study

**NCT07872007, newly posted October 13.** Korean investigators list a completed **72-person** randomized participant/investigator-masked study of smartphone **BELL-001 breathing-linked sounds** versus a sham app in adults with insomnia symptoms.

The single laboratory recording lasted **70 minutes**, with rest, active-use and passive stages. Primary outcomes are scalp EEG power and source-estimated connectivity across several frequency bands; heart-rate/variability measures are secondary. These are immediate physiology measurements, not overnight polysomnographic stage proportions, insomnia remission, daytime function or durable clinical benefit. Multiple EEG bands/connections also require a prespecified analysis and multiplicity appraisal.

Actual conduct was **November 18, 2025–February 18, 2026**; primary completion **February 11, 2026**. Registration happened after completion, with **no posted results** or harms rates. “Digital therapeutic” in the record is a product descriptor, not independently verified FDA authorization. Next: primary protocol chronology, full sham comparisons and clinically meaningful follow-up; no release date.

**Sources:** [Source 1](https://clinicaltrials.gov/study/NCT07872007).

**Remaining gaps:** Read current canonical scope, shared summaries/state and assigned topic notes. September 5–October 13 overlap preserves the September 12 full-review dates; October 6/9 entries were deduplicated. All pages of each bounded ClinicalTrials.gov query were downloaded, and named records plus selected relevant new/changed protocols were appraised. This is focused partial review, not a worldwide full literature/regulator/safety census; successful full-topic dates must remain unchanged.; Bounded query retrieved 136 records across 2 pages; incidental studies excluded. Named topic records refreshed: 5. Full older evidence, international registries, comprehensive harms and all original conference/podcast recordings remain gaps.; New condition-specific baseline remains incomplete. Selected inherited older pivotal sources and newly recovered formal programs were reviewed, without declaring the preceding 90-day/older trial corpus complete.

**Informal-source coverage:** Original ENLIGHTEN-6 anonymous fragmented-sleep account is saved once in GLP-1 with cross-link; no incidence inference. Exact-date insomnia Reddit searches produced irrelevant pregnancy/old matches and no distinct formal-development rumor selected. Insomnia podcast/talk full recordings and broader informal safety census remain incomplete.

[Full coverage record](../updates/2026-10-13_scheduled_research_update.md).


### Focused update — 2026-10-09

<span class="note-anchor" id="note-2026-09-16-smart-insomnia-baseline"></span>

#### Large pragmatic trial compares commonly used insomnia medicines

**Baseline context recovered October 9 — SMART, NCT07542756.** University of Pennsylvania/PCORI plans **1,200 adults with chronic insomnia** in a double-blind sequential multiple-assignment randomized trial. The registry reports **recruiting**, actual start **May 1, 2026**, and last update **September 16**; a mirror's later synchronization date is not a new recruitment event.

Arms include doxepin **3/6 mg**, zolpidem **5/10 mg**, trazodone **50/100 mg**, immediate-release melatonin **3/5 mg**, diphenhydramine **25/50 mg**, and placebo. Participants aged 64+ are excluded from the diphenhydramine arm. All receive sleep-hygiene education.

At one month, primary outcomes include **ISI response of at least eight points**, side-effect frequency/severity, and **FOSQ-10 daytime function**; responders are followed for durability/harms through six months. No results are posted. This trial does not endorse every studied medicine or erase off-label/guideline distinctions; symptoms and function are separate from sleep architecture. Estimated primary/final completion is **January 1, 2032**, not a guaranteed publication date.

**Sources:** [Primary source 1](https://clinicaltrials.gov/study/NCT07542756).

**Remaining gaps:** New condition baseline remains incomplete. Reviewed inherited hub, preceding 90-day development leads and selected older pivotal/contextual sources; October 6 findings deduplicated.; 93 named NCT records across the ten topics and ten discovery queries downloaded successfully through the ClinicalTrials.gov public API. Download is not a claim that all fields/safety/results were exhaustively appraised.; Focused review only. Do not advance full successful-check timestamps or label incomplete remaining searches as no news.; Broad insomnia discovery returned 673 records, first 100 downloaded; selected relevant records screened; much incidental oncology/psychiatry symptom language remains. Older drug label, CBT-I/digital durability and sleep-architecture safety census incomplete. Prior DARI-DREAM and COMISA-PEC not re-reported.

**Informal-source coverage:** Oct8 SOLIS-1 participant self-report and Oct2 Eloralintide weekly-trial posts contain insomnia/fatigue anecdotes; no population safety estimates or independent insomnia-drug milestone inferred. Original insomnia podcast/talk transcripts incomplete.

[Full coverage record](../updates/2026-10-09_scheduled_research_update.md).


### Focused update — 2026-10-06

<span class="note-anchor" id="note-2026-09-28-daridream"></span>

#### DARI-DREAM registration resolves the missing daytime-function study identifier

**Source/event date: September 28, 2026. Evidence: new trial registration recovered October 6.** DARI-DREAM / ID-078A306 supplies the missing daridorexant daytime-functioning study identifier. It plans 344 adults/older adults with insomnia, randomized 1:1 to daridorexant 50 mg or placebo for approximately three months, with triple masking and ten-day safety follow-up. Primary: subjective total sleep time at month 3. IDSIQ sleepiness and total daytime-impairment scores are secondary; home EEG is used to verify entry criteria.

NOT_YET_RECRUITING. September 2026 start remains estimated; November 2027 primary and December 2027 final completion are registry estimates. No results or trial safety estimates are posted. This closes registration uncertainty but does not verify the July forecast actual start or a new U.S. daytime-function claim. Adult insomnia approval is separate from this label-enabling research.

[Source 1](https://clinicaltrials.gov/api/v2/studies/NCT07843329) · [Source 2](https://clinicaltrials.gov/study/NCT07843329)

<span class="note-anchor" id="note-2026-10-05-comisapec"></span>

#### COMISA-PEC begins studying daridorexant before CPAP

**Source date: October 5, 2026; actual start: September 30. Evidence: registry recruitment update.** COMISA-PEC plans 150 French adults with AHI≥15 and ISI≥15, newly diagnosed and previously untreated with PAP/daridorexant. The open-label single-group strategy starts daridorexant before CPAP; the primary measure is nightly PAP use at four months, with 12-month use and daytime IDSIQ scores secondary. RECRUITING; estimated primary completion September 2028 and final September 2029. No efficacy/safety results. The outcome wording references untreated comparators, although the registered allocation is single-group; causal comparison and comparator selection need protocol clarification. This is not a randomized demonstration that medication improves adherence or treats airway obstruction, and creates no new U.S. indication.

[Source 1](https://clinicaltrials.gov/api/v2/studies/NCT07743931) · [Source 2](https://clinicaltrials.gov/study/NCT07743931)

<span class="note-anchor" id="note-2026-08-18-sleepymed"></span>

#### Small digital CBT-I versus zolpidem trial is older baseline context

**Historical baseline addition: online publication August 18, 2026; December issue date is not publication date.** jRCT2032230353 randomized 24 Japanese adults with persistent sleep-onset insomnia after sleep education to five weeks of unguided “IIIP MED: Sleepy Med” or zolpidem, followed for five more weeks. Subjective sleep-onset latency changed −20.65 minutes (95% CI −32.05 to −9.65; n11) versus −22.42 (−29.37 to −15.46; n13) at week 5; between-group P=.7729. Week-10 improvement persisted in nine digital participants, but the between-group comparison was also nonsignificant. No treatment-related AE was reported with the app; one zolpidem participant reported somnolence.

The tiny exploratory trial was underpowered: nonsignificance does not establish equivalence/noninferiority, remission or broad daytime benefit. A developer holds copyright on the app. No U.S. clearance was verified. Next confirmatory study/date is unannounced.

[Source 1](https://pubmed.ncbi.nlm.nih.gov/42623797/) · [Source 2](https://doi.org/10.1016/j.sleep.2026.109222)

**Coverage:** 2026-10-06: daridorexant daytime-function study October2026; direct named-drug registry search (30latest); 2026-10-06: insomnia digital CBT trial SeptemberOctober2026, PubMed42623797; 2026-10-06: Reddit DARIDREAM/insomnia trial leads

**Remaining gaps:** Pending condition baseline partially refreshed across preceding90days, new DARI-DREAM protocol, COMISA and older digital pilot. Existing ten-drug baseline and digital meta-analysis retained; no completed comprehensive baseline.; Full DARI-DREAM protocol/daytime-label intent and actual dosing remain unverified; full digital-pilot text blocked, PubMed XML read. Device/new-drug/digital worldwide census and original podcast sweep incomplete.

**Informal-source coverage:** No noteworthy attributable DARI-DREAM leak found; personal medication/CBTi discussion is not trial efficacy. Podcast recordings and all trial-participant threads incomplete.

[Full coverage record](../updates/2026-10-06_scheduled_research_update.md).


### CBT-I and validated digital therapy

**Development / U.S. status:** CBT-I has a strong AASM recommendation. Prescription Sleepio was cleared under K233577 on August 5, 2024, as an adjunct to usual care for chronic insomnia in adults; this does not validate every consumer app.

**Evidence / limitations:** The 336-person CrEDIT randomized trial had a 10-week primary assessment and follow-up through 24 weeks. The September 28, 2026 network meta-analysis included 96 randomized trials and found a 4.24-point ISI reduction with digital CBT versus pooled controls (95% CI 3.65–4.83 lower; moderate certainty). Direct comparisons and many study-quality assessments limit stronger rankings. [AASM guideline](https://pmc.ncbi.nlm.nih.gov/articles/PMC7853203/) · [FDA clearance](https://www.accessdata.fda.gov/cdrh_docs/pdf23/K233577.pdf) · [Evidence synthesis](https://doi.org/10.1186/s12916-026-05129-8)

**Next milestone:** Comparative delivery, durable remission/function and access; no firm readout date verified. [Original detailed coverage](12_sleep.md#digital-cbt-for-insomnia-retains-the-clearest-support-in-a-large-evidence-synthesis).

### Established insomnia medicines

**Development / U.S. status:** The selected baseline distinguishes approved formulations of doxepin, ramelteon, daridorexant, lemborexant, suvorexant, zolpidem, eszopiclone, zaleplon, temazepam and triazolam from off-label trazodone and mirtazapine. Approval and guideline recommendation are separate.

**Evidence / limitations:** Low-dose doxepin addresses maintenance, ramelteon addresses onset, and some other medicines have evidence for both. Historical controlled trials, formulation-specific labels, dependence/withdrawal, next-day impairment and serious class warnings remain in the [full medication baseline](12_sleep.md#sleep-insomnia-baseline). The baseline review date is October 3; it is not a complete surveillance check.

**Next milestone:** Meaningful comparative and longer-term results; no common next date verified. [AASM pharmacologic guideline](https://aasm.org/wp-content/uploads/2017/07/PharmacologicTreatmentofInsomnia.pdf) · [VA/DoD 2025 guideline](https://healthquality.va.gov/HEALTHQUALITY/guidelines/CD/insomnia/I-OSA-CPG_2025-Guideline_final_20250915.pdf)

### Investigational and non-U.S. programs

**Daridorexant pediatric / daytime-function studies:** Pediatric phase 2 NCT05423717 has a March 30 sponsor topline, not a pediatric approval or established durable safety result. The July 30 forecast daytime-functioning study was not matched to a verified start/registration in the earlier checks. [Full program details](12_sleep.md#expanded-sleep-therapy-baseline-september-12-2026).

**Vornorexant / Vorzzz:** Japanese approval and a published 52-week randomized-dose, open-label study do not establish U.S. approval or placebo-adjusted long-term benefit. No firm next U.S. milestone verified. [Full findings and safety](12_sleep.md#vornorexant-long-term-insomnia-study-published) · [Primary publication](https://pubmed.ncbi.nlm.nih.gov/42731338/).

**Neuro-DORA / lemborexant:** NCT06823752 measures short-term neurodegeneration biomarkers, not dementia prevention or long-term cognitive outcomes. Registry-estimated completion December 2027 is not a publication promise. [Full notes](12_sleep.md#neuro-dora-studies-sleep-treatment-and-neurodegeneration-biomarkers) · [Registry](https://clinicaltrials.gov/study/NCT06823752).

## Dated history

### October 3, 2026 — Topic organization

Created this condition-specific entry from existing sleep coverage. Earlier sources, program dates, historical findings and successful research-check timestamps were preserved. See the [organization record](../updates/2026-10-03_sleep_category_organization.md) and [original history](12_sleep.md#dated-history). This is a navigation and baseline projection, not a new medical-news event.