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Clarithromycin-mekanismer ved hypersomni-syndromer

16. juli 2026 opdateret af: Lynn Marie Trotti, Emory University

Antibiotikamedierede forbedringer i årvågenhed: Clarithromycins virkningsmekanismer ved hypersomnisyndromer

Formålet med denne undersøgelse er at evaluere en medicin kaldet clarithromycin til behandling af søvnighed under to relaterede tilstande, narkolepsi uden katapleksi og idiopatisk hypersomni. Undersøgelser har vist, at clarithromycin kan reducere søvnighed, men forskerne ved ikke, hvordan clarithromycin gør dette. Denne undersøgelse vil se på hjerneaktivitet (på magnetisk resonansbilleddannelse [MRI] og elektroencefalogram [EEG] hjernebølger), inflammation, bakterier, der lever i tarmen og cerebrospinalvæske, for bedre at forstå, hvordan clarithromycin kan reducere søvnighed. Denne undersøgelse vil rekruttere 92 deltagere, som vil blive randomiseret til at modtage clarithromycin eller placebo i 14 dage.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

Overdreven søvnighed i dagtimerne og lang søvn varighed er almindelige træk ved mange neurologiske lidelser, herunder myotonisk dystrofi, Parkinsons sygdom og hypersomnisyndromer i centralnervesystemet. Disse sidstnævnte syndromer er en gruppe af lidelser med overlappende kliniske fænotyper og, undtagen i tilfælde af narkolepsi på grund af hypokretinmangel (narkolepsi type 1), potentielt fælles patofysiologi.

Patologisk søvnighed i dagtimerne ved disse lidelser svækker arbejdsevnen, begrænser livskvaliteten og mere end fordobler risikoen for motorkøretøjer og andre ulykker. Fordi den underliggende årsag til størstedelen af ​​disse hypersomni-syndromer ikke er kendt, er behandlinger rettet mod at øge monoaminerg signalering involveret i vågent fremme. Alligevel kan mindst en fjerdedel af patienter med hypersomnisyndromer ikke opnå tilfredsstillende kontrol over symptomer med disse behandlinger, og handicap eller medicinske fravær er ofte nødvendige. Der er et klart behov for nye behandlinger for overdreven søvnighed i dagtimerne for at løse denne svigt af den nuværende standard for pleje.

I tidligere undersøgelser resulterede clarithromycin i signifikante, klinisk betydningsfulde forbedringer i sværhedsgraden af ​​søvnighed, søvnighedsrelaterede begrænsninger i forlængede daglige aktiviteter og søvnighedsrelateret livskvalitet. Lange søvnvarigheder og søvninerti, begge underordnede symptomer på hypersomniforstyrrelser, der bidrager til funktionsnedsættelser, blev også forbedret med clarithromycin.

Hypotese: Clarithromycin vil reducere overdreven søvnighed og andre symptomer på hypersomniforstyrrelser, målt ved selvrapportering og objektiv test.

Mål 1: At identificere centralnervesystemets mediatorer af clarithromycins evne til at fremme vågenhed og reducere søvnighed blandt patienter med centrale hypersomnisyndromer.

Hypotese 1a: Ændringer i cerebrospinalvæske (CSF) forstærkning af gamma-aminosmørsyre-A (GABA-A) receptorfunktion in vitro vil være forbundet med forbedringer i selvrapporteret og objektivt målt søvnighed.

Hypotese 1b: Ændringer i funktionel forbindelse vil være forbundet med forbedringer i selvrapporteret og objektivt målt søvnighed.

Formål 2: At undersøge ekstra-neuronale mekanismer, hvorved clarithromycin kan reducere søvnighed, herunder ændringer i systemisk inflammation og ændringer i gastrointestinal mikrobiota-sammensætning, hos patienter med centrale hypersomni-syndromer.

Hypotese 2a: Forbedring af søvnighed med clarithromycinbrug vil være positivt forbundet med reduktioner i systemisk inflammation, især reduktioner i niveauer af tumornekrosefaktor-alfa (TNFα).

Hypotese 2b: Forbedring af søvnighed ved brug af clarithromycin vil være positivt korreleret med modulering af gastrointestinal dysbiose.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

83

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Forenede Stater
    • Georgia
      • Atlanta, Georgia, Forenede Stater, 30329
        • Emory Sleep Center

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 60 år (Voksen)

Tager imod sunde frivillige

Ingen

Beskrivelse

Inklusionskriterier:

  • diagnose af idiopatisk hypersomni eller narkolepsi type 2
  • alder 18-60
  • fri for vækningsfremmende medicin, søvnig på trods af nuværende vågne-fremmende medicin eller villig til at seponere den nuværende vågne-fremmende medicin i mindst 5 halveringstider forud for baseline-foranstaltninger
  • fri for præ- eller probiotiske kosttilskud i mindst seks måneder forud for baseline-foranstaltninger

Ekskluderingskriterier:

  • andre potentielle årsager til hypersomnolens, herunder moderat eller svær søvnapnø, alvorlig periodisk bevægelsesforstyrrelse i lemmer med ophidselse, ukontrollerede stofskifteforstyrrelser, hypokretinmangel eller katapleksi
  • kontraindikation for clarithromycin
  • kontraindikation til nogen af ​​undersøgelsesprocedurerne

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Grundvidenskab
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Dobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Clarithromycin
Deltagere i denne undersøgelsesarm vil modtage clarithromycin i 14 dage.
Medicin: Clarithromycin
Clarithromycin vil blive doseret som 500 mg to gange dagligt, én gang ved opvågning og én gang med frokost, i 14 dage.
Andre navne:
  • Biaxin
Placebo komparator: Placebo
Deltagerne i denne undersøgelsesarm vil modtage en placebo, der matcher clarithromycin i 14 dage.
Medicin: Placebo
Et placebo, der matcher clarithromycin, vil blive doseret som 500 mg to gange dagligt, én gang ved opvågning og én gang med frokost, i 14 dage.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Change in Epworth Sleepiness Scale (ESS) Score
Tidsramme: Day -1, Day 14
The Epworth Sleepiness Scale asks participants to respond to 8 scenarios with how likely they are to fall asleep on a 4-point scale where 0 = "would never doze" and 3 = "high chance of dozing". Total scores range from 0 to 24 where higher scores indicate a higher chance of falling asleep during daytime activities. The change in ESS score is obtained by subtracting the total score at Day 14 from the baseline score. Scores above 0 mean that the mean score at Day 14 was lower than the mean score at Baseline, indicating less sleepiness.
Day -1, Day 14
Change in Maintenance of Wakefulness Test (MWT) for Sleep Latency
Tidsramme: Day -1, Day 14
The MWT polysomnographic procedure for sleep latency examines how well participants stay awake during several trials where participants relax in a quiet room for 40 minutes. One study found the mean sleep latency among persons without a sleep disorder to be 35.2 minutes. The change from baseline is calculated as baseline sleep latency minus sleep latency at Day 14, in minutes. Positive values result when the duration of sleep latency at Day 14 is lower than at Baseline.
Day -1, Day 14
Change in Gamma-aminobutyric Acid Receptor A (GABA-A) Potentiation
Tidsramme: Day -1, Day 14
Cerebrospinal fluid (CSF) is drawn to determine the change in levels of GABA-A potentiation between the study arms. The difference between measured current with GABA alone and the current measured with GABA + CSF yields a measure of potentiation for each CSF sample in each condition. The change from baseline is calculated as the baseline value minus the value at Day 14.
Day -1, Day 14
Change in Default Mode Network (DMN) Connectivity
Tidsramme: Day -2, Day 13
The default mode network (DMN) consists of a group of highly correlated brain regions most active during quiet rest, while the task positive network (TPN) is the brain network activated for goal-directed tasks. DMN connectivity changes with sleep states and it is increasingly implicated in the symptomatology of sleepiness. During resting state, sleep deprived participants demonstrate reduced static connectivity with the DMN. Changes in DMN between the Baseline 1 (Day - 2) and Day 13 visits are compared between treatment groups, particularly using quasi-periodic patterns (QPPs), which interrogate network-level connectivity on a dynamic scale. Preservation of the temporal dimension provides more insight into how this spatiotemporal network propagates across condition and pathology. The DMN/TPN QPP correlation is reported.
Day -2, Day 13
Change in Tumor Necrosis Factor - Alpha (TNF-α)
Tidsramme: Day -1, Day 14
Blood samples are used to determine the change in levels of TNF-α between the study arms. TNF-α is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness.
Day -1, Day 14
Change in Gastrointestinal Microbiome Composition
Tidsramme: Day -1, Day 14
Changes in microbiome composition, as measured by alpha diversity using the Shannon Index, via 16S ribosomal ribonucleic acid (rRNA) sequencing results are compared between study arms. The Shannon Index measures both abundance and evenness of microbial species, values of 0 indicate that a community has only one species. The higher the value the higher the diversity of species in a particular community. Change from baseline is calculated by subtracting the Day 14 value from the value at Baseline. Numbers greater than 0 indicate that the Day 14 Shannon index value is lower than at Baseline.
Day -1, Day 14

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
On-Treatment Sleep Duration
Tidsramme: Day 1 through Day 14
Participants log when they go to bed and when they wake up in order to calculate the number of minutes spent sleeping. The average duration of sleep across 14 days is compared between study arms.
Day 1 through Day 14
Change in Fatigue Severity Scale (FSS) Score
Tidsramme: Day -1, Day 14
Fatigue severity is measured with the Fatigue Severity Scale (FSS). The FSS is a 9-item instrument where responses are on a scale of 1 to 7 where 1 = "disagree" and 7 = "agree". Total scores range from 9 to 63 where higher scores indicate greater fatigue. The change in FSS score is obtained by subtracting the total score at Day 14 from the Baseline score. Scores above 0 signify that the mean score at Day 14 was lower than the mean score at Baseline, indicating decreased fatigue.
Day -1, Day 14
Change in Multidimensional Fatigue Inventory (MFI-20) Score
Tidsramme: Day -1, Day 14
The MFI-20 is a 20-item instrument assessing fatigue severity. Responses are on a 5-point scale where 1 = "yes, that is true" and 5 = "no, that is not true". Positively phrased items are reverse scored so that the total score ranges from 20 to 100 where higher scores indicate greater severity of fatigue. The change in MFI-20 score is obtained by subtracting the total score at Day 14 from the Baseline score. Scores above 0 signify that the mean score at Day 14 was lower than the mean score at Baseline, indicating decreased fatigue.
Day -1, Day 14
Change in Sleep Inertia Questionnaire (SIQ) Score
Tidsramme: Day -1, Day 14
The SIQ is an instrument with 21 items with responses on a 5-point scale where 1 = "not at all" and 5 = "all the time". Two additional questions relate to how much time it takes for the respondent to wake up in the morning. Total scores range from 21 to 105 and higher scores indicate increased difficulty from tiredness. The change in SIQ score is obtained by subtracting the total score at Day 14 from the baseline score. Scores above 0 signify that the mean score at Day 14 was lower than the mean score at Baseline, indicating reduced difficulty awakening.
Day -1, Day 14
On-Treatment Sleep Inertia Likert Scale
Tidsramme: Day 1 through Day 14
Sleep inertia is measured with a single item on a 10-point Likert scale asking participants how difficult it was for them to wake up in the morning, where 1 = "not difficult at all" and 10 = "very difficult". The average scores across 14 days are compared between study arms.
Day 1 through Day 14
Change in Interleukin 1 Alpha (IL-1α)
Tidsramme: Day -1, Day 14
Blood samples are used to determine the change in levels of IL-1α between the study arms. IL-1α is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness. The change in IL-1α is obtained by subtracting the IL-1α level at Day 14 from the Baseline level.
Day -1, Day 14
Change in Interleukin 1 Beta (IL-1β)
Tidsramme: Day -1, Day 14
Blood samples are used to determine the change in levels of IL-1β between the study arms. IL-1β is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness. The change in IL-1β is obtained by subtracting the IL-1β level at Day 14 from the Baseline level.
Day -1, Day 14
Change in Interleukin 2 (IL-2)
Tidsramme: Day -1, Day 14
Blood samples are used to determine the change in levels of IL-2 between the study arms. IL-2 is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness. The change in IL-2 is obtained by subtracting the IL-2 level at Day 14 from the Baseline level.
Day -1, Day 14
Change in Interleukin 6 (IL-6)
Tidsramme: Day -1, Day 14
Blood samples are used to determine the change in levels of IL-6 between the study arms. IL-6 is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness. The change in IL-6 is obtained by subtracting the IL-6 level at Day 14 from the Baseline level.
Day -1, Day 14
Change in Interleukin (IL-8)
Tidsramme: Day -1, Day 14
Blood samples are used to determine the change in levels of IL-8 between the study arms. IL-8 is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness. The change in IL-8 is obtained by subtracting the IL-8 level at Day 14 from the Baseline level.
Day -1, Day 14
Change in Interleukin (IL-15)
Tidsramme: Day -1, Day 14
Blood samples are used to determine the change in levels of IL-15 between the study arms. IL-15 is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness. The change in IL-15 is obtained by subtracting the IL-15 level at Day 14 from the Baseline level.
Day -1, Day 14
Change in Interleukin (IL-18)
Tidsramme: Day -1, Day 14
Blood samples are used to determine the change in levels of IL-18 between the study arms. IL-18 is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness. The change in IL-18 is obtained by subtracting the IL-18 level at Day 14 from the Baseline level.
Day -1, Day 14
Change in Tumor Necrosis Factor Beta (TNF-β)
Tidsramme: Day -1, Day 14
Blood samples are used to determine the change in levels of TNF-β between the study arms. TNF-β is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness. The change in TNF-β is obtained by subtracting the TNF-β level at Day 14 from the Baseline level.
Day -1, Day 14
Change in Interferon Alpha (INF-α2a)
Tidsramme: Day -1, Day 14
Blood samples are used to determine the change in levels of INF-α2a between the study arms. INF-α2a is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness. The change in INF-α2a is obtained by subtracting the INF-α2a level at Day 14 from the Baseline level.
Day -1, Day 14
Change in Functional Outcomes of Sleep Questionnaire (FOSQ) Score
Tidsramme: Day -1, Day 14
The FOSQ is a 30-item instrument assessing how sleepiness impacts daily activities. There are five subscales assessing General Productivity, Activity Level, Vigilance, Social Outcomes, and Intimate and Sexual Relationships. Items are scored on a 4-point scale where 1 = extreme difficulty and 4 = no difficulty. Subscale scores are obtained by calculating the mean score for the items in that subscale and each can range from 1 to 4, where higher scores indicate less difficulty due to sleepiness. A total score is obtained by calculating the means of the subscale scores and multiplying that by the number of subscales with a score. The total score ranges from 5 to 20 and higher scores indicate less difficulty from sleepiness. The change in FOSQ score is obtained by subtracting the total score at Day 14 from the Baseline score. Scores below 0 signify that the mean score at Day 14 was higher than the mean score at Baseline, indicating reduced difficulty from sleepiness.
Day -1, Day 14
Change in Hypersomnia Severity Index (HSI)
Tidsramme: Day -1, Day 14
The HSI is a 9-item instrument assessing the severity of excessive sleepiness (hypersomnolence). Items are scored on a Likert scale where 0 = not at all and 4 = very much. Total scores range from 0 to 36 and higher scores indicate greater severity of symptoms of hypersomnia. The change from baseline is calculated as the baseline score minus the score at Day 14. The change in HSI score is obtained by subtracting the total score at Day 14 from the baseline score. Scores above 0 signify that the mean score at Day 14 was lower than the mean score at Baseline, indicating reduced severity of hypersomnia symptoms.
Day -1, Day 14
Change in MRI Functional Connectivity
Tidsramme: Day -2, Day 13
For functional connectivity analyses, each functional scan is parceled into the 246 regions of interest (ROIs), spanning Yeo's 7 networks contained in the Brainnetome Atlas and mean timecourse is calculated for each group. Pearson correlations between each pair of ROIs are calculated, to determine the strength of functional connectivity between each pair of regions and inter/intra-network. This yields a functional connectivity matrix for each functional scan (at both a subject- and group-level). These correlation matrices are Fischer z-transformed and averaged across each condition to create a mean functional connectivity matrix for each condition. Here, the average default mode network (DMN) connectivity is reported. Z-scores have a mean of 0 and scores higher than 0 indicate increased functional connectivity. The change from Baseline is calculated by subtracting the Day 13 score from the score at Day -2. Values lower than 0 mean that the Day 13 score was higher than at baseline.
Day -2, Day 13
Change in MRI Task Performance - N-Back Accuracy
Tidsramme: Day -2, Day 13
Participants complete a working memory task during functional magnetic resonance imaging (fMRI). The change in task performance is measured as accuracy during 3 different levels of back tasks (0-back, 1-back, and 2-back), from baseline to on-treatment (Day 13). The 0-back test has participants respond to a prespecified stimulus and is a control condition. The 1-back involves remembering and responding to a prior stimulus, while a stimulus two trials earlier is responded to with the 2-back. The change in the percentage of correct responses is obtained by subtracting the percentage at Day 14 from the Baseline percentage. Values below 0 signify that the mean percent accuracy at Day 14 was higher than the mean percent accuracy at Baseline, indicating increased accuracy.
Day -2, Day 13
Change in MRI Task Performance - N-Back Reaction Time
Tidsramme: Day -2, Day 13
Participants complete a working memory task during functional magnetic resonance imaging (fMRI). he change in task performance is measured as reaction time during 3 different levels of back tasks (0-back, 1-back, and 2-back), from baseline to on-treatment (Day 13). The 0-back test has participants respond to a prespecified stimulus and is a control condition. The 1-back involves remembering and responding to a prior stimulus, while a stimulus two trials earlier is responded to with the 2-back. The change in the reaction time of responses is obtained by subtracting the time at Day 14 from the Baseline time. Scores above 0 signify that the mean time at Day 14 was lower than the mean time at Baseline, indicating faster reaction time.
Day -2, Day 13

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Emory University

Samarbejdspartnere

National Institute of Neurological Disorders and Stroke (NINDS)

Efterforskere

  • Ledende efterforsker: Lynn Marie Trotti, MD, MSc, Emory University

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

4. september 2019

Primær færdiggørelse (Faktiske)

18. juni 2025

Studieafslutning (Faktiske)

18. juni 2025

Datoer for studieregistrering

Først indsendt

17. juli 2019

Først indsendt, der opfyldte QC-kriterier

18. juli 2019

Først opslået (Faktiske)

19. juli 2019

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

7. august 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

16. juli 2026

Sidst verificeret

1. juli 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • IRB00108681
  • 1R01NS111280 (U.S. NIH-bevilling/kontrakt)
  • 2025P011204 (Anden identifikator: Emory IRB)

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

JA

IPD-planbeskrivelse

Efter afidentifikation vil individuelle patientdata indsamlet under forsøget, der ligger til grund for resultaterne rapporteret i artiklen, være tilgængelige for at blive delt med andre forskere.

IPD-delingstidsramme

Data vil være tilgængelige for deling begyndende 3 måneder efter artiklens udgivelse og slutter 3 år efter artiklens offentliggørelse. Der vil blive gjort rimelige forsøg på at imødekomme anmodninger efter 3 år.

IPD-delingsadgangskriterier

Individuelle deltagerdata vil være tilgængelige for deling med forskere, der giver et metodisk forsvarligt forslag, og med andre enheder, der giver et klart rationale for databrug. Data vil blive delt til analyser for at nå målene med det godkendte forslag. Forslag til brug af data skal rettes til lbecke2@emory.edu.

IPD-deling Understøttende informationstype

  • STUDY_PROTOCOL

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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