Intranasal Esketamine-dexmedetomidine Combination in Patients With Postherpetic Neuralgia
Efficacy of Intranasal Esketamine-dexmedetomidine Combination in Patients With Postherpetic Neuralgia: a Randomized, Double-blind, Active Drug-controlled Trial
Postherpetic neuralgia (PHN) is a chronic neuropathic pain syndrome suffered by patients with herpes zoster and often adversely affect patients' normal lives, leading to declines in sleep and quality of life. Ketamine/esketamine has been used for treatment of chronic pain but may produce adverse psychiatric reactions at slightly higher doses, including dissociative symptoms, hallucinations, and nightmares; the sedative effect of dexmedetomidine helps mitigate its psychiatric side effects. A previous study in orthopedic surgery patients also showed that dexmedetomidine combined with esketamine can significantly improve perioperative analgesia and sleep quality. The investigators hypothesize that intranasal administration of dexmedetomidine combined with esketamine in patients with postherpetic neuralgia can improve analgesic efficacy.
Panoramica dello studio
Stato
Stato
Condizioni
Condizioni
Intervento / Trattamento
Intervento / Trattamento
Descrizione dettagliata
Postherpetic neuralgia (PHN) is a chronic neuropathic pain syndrome suffered by patients with herpes zoster. The typical feature of PHN is deep burning pain in the affected unilateral dermatome, often accompanied by stabbing pain and itching, persisting for more than 3 months after the initial onset of herpes zoster. The incidence of PHN among patients with herpes zoster is approximately 10-20%. The chronic pain symptoms of PHN often adversely affect patients' normal lives, leading to declines in sleep and quality of life. Approximately 50% of PHN patients have sleep disturbances. These ultimately affect cognitive function and mental health.
Ketamine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist and has long been used as a dissociative anesthetic. At subanesthetic doses, ketamine exhibits analgesic and antihyperalgesic effects. Guidelines recommend low-dose ketamine infusion for the treatment of chronic pain. Esketamine is the more potent right-handed enantiomer of ketamine, with stronger affinity for the NMDA receptor; its potency is approximately twice that of ketamine, and the incidence of adverse psychiatric reactions is lower in clinical use. Intranasal esketamine has been approved by the FDA for the treatment of adults with treatment-resistant depression and represents a more non-invasive route of administration.
Dexmedetomidine is a highly selective α2-adrenergic receptor agonist with sedative, analgesic, and anxiolytic effects. Dexmedetomidine acts on the locus coeruleus, inhibiting the release of norepinephrine from neurons in the locus coeruleus and the activity of the medullary-spinal descending neural pathways, thereby producing sedative and analgesic effects. In perioperative management, dexmedetomidine is widely used for postoperative adjuvant analgesia; it can also improve patients' sleep, producing a state resembling non-rapid eye movement sleep. Intranasal dexmedetomidine can be safely used in adults and children and is currently widely used for pediatric procedural sedation and preoperative medication.
Ketamine/esketamine can produce adverse psychiatric reactions at slightly higher doses, including dissociative symptoms, hallucinations, and nightmares; the sedative effect of dexmedetomidine helps mitigate its psychiatric side effects. A previous study in orthopedic surgery patients also showed that dexmedetomidine combined with esketamine can significantly improve perioperative analgesia and sleep quality. The investigators hypothesize that intranasal administration of dexmedetomidine combined with esketamine in patients with postherpetic neuralgia can improve analgesic efficacy.
Tipo di studio
Tipo di studio
Iscrizione (Stimato)
Iscrizione
Fase
Fase
- Fase 4
Contatti e Sedi
Contatto studio
Contatto studio
- Nome: Zeng-Mao Lin
- Numero di telefono: +86 010-83572784
- Email: linzengmao@163.com
Luoghi di studio
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Beijing Municipality
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Beijing, Beijing Municipality, Cina, 100034
- Peking University First Hospital
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Contatto:
- Dong-Xin Wang
- Numero di telefono: +86 010-83572784
- Email: wangdongxin@hotmail.com
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Criteri di partecipazione
Criteri di ammissibilità
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion Criteria:
- Age ≥ 50 years.
- Diagnosis of postherpetic neuralgia (PHN) requiring pharmacological analgesia, with a pain score ≥ 4 on the numerical rating scale (NRS).
- Provision of written informed consent.
Exclusion Criteria:
- Unsuitability for intranasal administration due to nasal disorders (e.g., rhinitis, nasal polyps, or nasal obstruction from any cause).
- Inability to communicate owing to severe dementia, coma, or a language barrier.
- History of schizophrenia, epilepsy, Parkinson's disease, or myasthenia gravis.
- Previous diagnosis of sleep apnoea, or high risk of moderate-to-severe sleep apnoea on the STOP-Bang assessment, or body mass index > 30 kg/m².
- History of hyperthyroidism or phaeochromocytoma.
- Left ventricular ejection fraction (LVEF) < 30%; or sick sinus syndrome, severe sinus bradycardia (heart rate < 50 bpm), or second-degree or higher atrioventricular block without an implanted pacemaker; or systolic blood pressure < 90 mmHg before enrolment.
- Severe hepatic impairment (Child-Pugh class C); severe renal impairment requiring dialysis; or any ongoing life-threatening condition (e.g., myocardial infarction, cerebrovascular accident, transient ischaemic attack, or coronary stenting within the previous 3 months; active myocardial ischaemia; severe valvular disease; or end-stage renal disease not receiving dialysis).
- Hypersensitivity to dexmedetomidine and/or esketamine.
- Participation in another clinical trial, or any other condition that, in the investigator's opinion, makes the patient unsuitable for inclusion.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Quadruplicare
Numero di armi
Armi e interventi
Gruppo di partecipanti / ArmGruppo di partecipanti / Arm |
Intervento / TrattamentoIntervento / Trattamento |
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Sperimentale: DEX-ESK group
For each administration: dexmedetomidine (1 spray = 0.05 ml = 25 μg) is administered as one spray into each nostril; after 1 minute, esketamine (1 spray = 0.05 ml = 1.25 mg) is administered alternately into each nostril, 4 sprays per nostril. Esketamine administration is repeated every 5 minutes until a total dose of 0.3 mg/kg is reached (using the number of sprays closest to the predetermined dose). If a dose is not tolerated, one administration may be omitted. Administer once daily for 4 consecutive days, with the same administration method as above. |
For each administration: dexmedetomidine (1 spray = 0.05 ml = 25 μg) is administered as one spray into each nostril; after 1 minute, esketamine (1 spray = 0.05 ml = 1.25 mg) is administered alternately into each nostril, 4 sprays per nostril. Esketamine administration is repeated every 5 minutes until a total dose of 0.3 mg/kg is reached (using the number of sprays closest to the predetermined dose). If a dose is not tolerated, one administration may be omitted. Administer once daily for 4 consecutive days, with the same administration method as above.
Altri nomi:
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Comparatore attivo: ESK group
For each administration: placebo (0.9% saline; 1 spray = 0.05 ml) is administered as one spray into each nostril; after 1 minute, esketamine (1 spray = 0.05 ml = 1.25 mg) is administered alternately into each nostril, 4 sprays per nostril. Esketamine administration is repeated every 5 minutes until a total dose of 0.3 mg/kg is reached (using the number of sprays closest to the predetermined dose). If a dose is not tolerated, one administration may be omitted. Administer once daily for 4 consecutive days, with the same administration method as above. |
For each administration: placebo (0.9% saline; 1 spray = 0.05 ml) is administered as one spray into each nostril; after 1 minute, esketamine (1 spray = 0.05 ml = 1.25 mg) is administered alternately into each nostril, 4 sprays per nostril. Esketamine administration is repeated every 5 minutes until a total dose of 0.3 mg/kg is reached (using the number of sprays closest to the predetermined dose). If a dose is not tolerated, one administration may be omitted. Administer once daily for 4 consecutive days, with the same administration method as above.
Altri nomi:
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Sum of pain intensity difference (SPID) within 7 days after the first administration
Lasso di tempo: Within 7 days after the first administration
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Follow-up time points: before each administration (Days 1, 2, 3, and 4 of enrollment; face-to-face follow-up); on Days 1, 2, and 3 after the last administration (Days 5, 6, and 7 of enrollment; telephone follow-up at the same time of day as drug administration). Pain intensity: the patient's NRS pain score over the past 24 hours is recorded (0-10; 0 = no pain at all, 10 = the worst pain imaginable). Sum of pain intensity difference (SPID): calculated as the sum of (baseline NRS score - NRS score at each scheduled daily follow-up) within 7 days after the first administration (i.e., 3 days after the last treatment). |
Within 7 days after the first administration
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Misure di risultato secondarie
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Sum of pain intensity difference (SPID) during Weeks 2 to 12 after the first administration
Lasso di tempo: During Weeks 2 to 12 after the first administration
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Follow-up time points: once weekly after the last administration until Week 12 of enrollment (Days 14, 21, 28, 35, 42, 49, 56, 63, 70, 77, and 84 of enrollment; telephone follow-up). Pain intensity: the patient's NRS pain score over the past 24 hours is recorded (0-10; 0 = no pain at all, 10 = the worst pain imaginable). Sum of pain intensity difference (SPID): calculated as the sum of (baseline NRS score - NRS score at each scheduled weekly follow-up) during Weeks 2 to 12 after the first administration. |
During Weeks 2 to 12 after the first administration
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Change from baseline in ZBPI chronic pain and impact scores within 3 months after treatment
Lasso di tempo: Up to 3 months after the first administration
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Follow-up time points: Days 7 and 14 after the first administration (telephone follow-up); Months 1, 2, and 3 after the first administration (Days 28, 56, and 84 of enrollment; telephone follow-up). Severity of chronic pain and its impact on patients: assessed using the Zoster Brief Pain Inventory (ZBPI, Appendix 7). Pain severity is rated from 0 to 10, with higher scores indicating greater pain severity; pain interference is rated from 0 to 10 across 7 domains, with higher scores indicating greater interference with daily functioning. Within 3 months after the first dose |
Up to 3 months after the first administration
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Collaboratori e investigatori
Sponsor
Sponsor
Investigatori
Investigatori
- Investigatore principale: Dong-Xin Wang, MD, PhD, Peking University First Hospital
Pubblicazioni e link utili
Pubblicazioni generali
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- Lee KH, Lee SJ, Park JH, Kim SH, Lee H, Oh DS, Kim YH, Park YH, Kim H, Lee SE. Analgesia for spinal anesthesia positioning in elderly patients with proximal femoral fractures: Dexmedetomidine-ketamine versus dexmedetomidine-fentanyl. Medicine (Baltimore). 2020 May;99(20):e20001. doi: 10.1097/MD.0000000000020001.
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- Gabriel RA, Swisher MW, Sztain JF, Furnish TJ, Ilfeld BM, Said ET. State of the art opioid-sparing strategies for post-operative pain in adult surgical patients. Expert Opin Pharmacother. 2019 Jun;20(8):949-961. doi: 10.1080/14656566.2019.1583743. Epub 2019 Feb 27.
- Zhang Y, Cui F, Ma JH, Wang DX. Mini-dose esketamine-dexmedetomidine combination to supplement analgesia for patients after scoliosis correction surgery: a double-blind randomised trial. Br J Anaesth. 2023 Aug;131(2):385-396. doi: 10.1016/j.bja.2023.05.001. Epub 2023 Jun 9.
- Dworkin RH, Gnann JW Jr, Oaklander AL, Raja SN, Schmader KE, Whitley RJ. Diagnosis and assessment of pain associated with herpes zoster and postherpetic neuralgia. J Pain. 2008 Jan;9(1 Suppl 1):S37-44. doi: 10.1016/j.jpain.2007.10.008.
- Gabutti G, Valente N, Kuhdari P, Lupi S, Stefanati A. Prevention of herpes zoster and its complications: from the clinic to the real-life experience with the vaccine. J Med Microbiol. 2016 Dec;65(12):1363-1369. doi: 10.1099/jmm.0.000386. Epub 2016 Nov 4.
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- Volpi A, Gatti A, Pica F, Bellino S, Marsella LT, Sabato AF. Clinical and psychosocial correlates of post-herpetic neuralgia. J Med Virol. 2008 Sep;80(9):1646-52. doi: 10.1002/jmv.21254.
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Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Dolore
- Manifestazioni neurologiche
- Malattie del sistema nervoso
- Malattie neuromuscolari
- Malattie del sistema nervoso periferico
- Nevralgia
- Condizioni patologiche, segni e sintomi
- Segni e sintomi
- Nevralgia, posterpetica
- Preparati farmaceutici
- Soluzioni cristalloidi
- Soluzioni isotoniche
- Soluzioni
- Esketamina
- Soluzione salina
Altri numeri di identificazione dello studio
Altri numeri di identificazione dello studio
- 2026R0576
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