Tirzepatide in Idiopathic Intracranial Hypertension Trial

Официальное название

A Phase IV Placebo-controlled Single Center Trial for Tirzepatide in Idiopathic Intracranial Hypertension Trial (TIIHT)

Обзор

This will be a randomized, double-blind, parallel, placebo-controlled trial of 60 participants. The primary analysis will be a statistical comparison of the estimates of the mean difference in the 12-month change in intracranial pressure (ICP) between participants assigned to the tirzepatide and Placebo arms in 1:1 randomization using the intention-to-treat (ITT) population. Hypothesis testing will be performed using analysis of covariance (ANCOVA), with the treatment indicator as the independent variable and the 12-month change in ICP as the dependent variable. Models will include baseline ICP as a covariate. This primary endpoint will use a significance level of 0.05 to declare significance.

Вмешательства

• Препарат Tirzepatide
  Dosage Treatment time 2.5mg/0.5mL: 4 Weeks 5mg/0.5mL: 4 Weeks 7.5mg/0.5mL: 4 Weeks 10mg/0.5mL: 4 Weeks 12.5mg/0.5mL: 4 weeks 15mg/0.5 mL: 7 Months
• Препарат Tirzepatide Placebo
  Dosage Treatment time 2.5mg/0.5mL: 4 Weeks 5mg/0.5mL: 4 Weeks 7.5mg/0.5mL: 4 Weeks 10mg/0.5mL: 4 Weeks 12.5mg/0.5mL: 4 weeks 15mg/0.5 mL: 7 Months

Первичные конечные точки

• Change in intracranial pressure in Idiopathic Intracranial Hypertension (IIH) patients [Срок оценки: From enrollment to end of treatment at 12 months]

Вторичные конечные точки (3)

• Retinal Nerve Fiber Layer (RNFL) Thickness on optical coherence tomograhy (OCT) [Срок оценки: From enrollment to end of treatment at 12 months]
• Change in Frisen papilledema grade on fundus photography [Срок оценки: From enrollment to the end of treatment at 12 months]
• Change in perimetric mean deviation [Срок оценки: From enrollment to end of treatment at 12 months]

Критерии участия

Критерии включения

• Signs and symptoms of increased intracranial pressure:

• headaches, tinnitus, visual obscurations, papilledema;
• absence of localizing findings on neurological examination (except for VI nerve palsy);
• no secondary causes identified on imaging, e.g., hydrocephalus, space- occupying lesion;
• elevated lumbar puncture (LP) opening pressure (OP) ≥25 cm H2O in lateral decubitus position with legs extended (>= (≥ 20cm H2O if one of the following is present: pulse synchronous tinnitus, abducens palsy, Frisen grade II papilledema, transverse venous sinus stenosis, partially empty sella or enlarged optic nerve sheath on magnetic resonance imaging (MRI);
• the patient is awake and alert.
• BMI ≥30 kg/m2
• Age 18-60 years of age
• Unilateral or bilateral papilledema
• Able to provide informed consent
• Women of child-bearing age must use birth control (non-oral contraceptive method or add a barrier method of contraception).

Критерии исключения

• Previous bariatric surgery
• Prior intervention for high ICP including optic nerve sheath fenestration (ONSF), venous stenting and/or shunting
• Taking another GLP-1 agonist, another drug that can interfere with the GLP-1 agonist, or any other anti-obesity medication
• History of pancreatitis, personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN2), history of gallbladder disease, ulcerative colitis, Crohn's disease, or history of hypersensitivity reaction in response to the drug
• Pregnancy or planning a pregnancy in the next 12 months or currently breastfeeding
• Other disorders causing visual loss and/or anomalous optic nerve
• Taking another medication to lower ICP in IIH (if previously taking another medication for ICP must be off this medication for at least 30 days prior to enrollment)
• No change in headache medications in the past 60 days
• Venous sinus thrombosis on magnetic resonance venography (MRV)
• Papilledema Frisen Grade III, IV or fulminant IIH
• Mean perimetric deviation ≤ -7 dB
• CSF contents outside of normal limits
• Uncontrolled hypertension (≥140mmHg/90 mmHg)
• Anemia (hemoglobin \[Hgb\] ≤ 8.0g/dL)
• Diagnosed sleep apnea with continuous positive airway pressure (CPAP) use
• Exposure to a drug, substance, or disorder that has been associated with elevation of intracranial pressure within 2 months of diagnosis such as lithium, vitamin A, various cyclines
• eGFR < 30 ml/min/1.73m2
• Type II diabetes

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Duke University Medical Center — Durham

Публикации

• Spitze A, Lam P, Al-Zubidi N, Yalamanchili S, Lee AG. Controversies: Optic nerve sheath fenestration versus shunt placement for the treatment of idiopathic intracranial hypertension. Indian J Ophthalmol. 2014 Oct;62(10):1015-21. doi: 10.4103/0301-4738.146012. PMID 25449938
• Chen J, Wall M. Epidemiology and risk factors for idiopathic intracranial hypertension. Int Ophthalmol Clin. 2014 Winter;54(1):1-11. doi: 10.1097/IIO.0b013e3182aabf11. No abstract available. PMID 24296367
• Mollan SP, Ali F, Hassan-Smith G, Botfield H, Friedman DI, Sinclair AJ. Evolving evidence in adult idiopathic intracranial hypertension: pathophysiology and management. J Neurol Neurosurg Psychiatry. 2016 Sep;87(9):982-92. doi: 10.1136/jnnp-2015-311302. Epub 2016 Feb 17. PMID 26888960
• Miah L, Strafford H, Fonferko-Shadrach B, Hollinghurst J, Sawhney IMS, Hadjikoutis S, Rees MI, Powell R, Lacey A, Pickrell WO. Incidence, Prevalence, and Health Care Outcomes in Idiopathic Intracranial Hypertension: A Population Study. Neurology. 2021 Feb 22;96(8):e1251-e1261. doi: 10.1212/WNL.0000000000011463. PMID 33472926
• Mollan SP, Aguiar M, Evison F, Frew E, Sinclair AJ. The expanding burden of idiopathic intracranial hypertension. Eye (Lond). 2019 Mar;33(3):478-485. doi: 10.1038/s41433-018-0238-5. Epub 2018 Oct 24. PMID 30356129

Идентификаторы

NCT: NCT07191873 · Pro00117470

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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