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GLP-1 Receptor Agonist in Primary Intracerebral Hemorrhage: A Phase 2 Randomized Trial (GLICH)

22 mai 2026 mis à jour par: Dr. IP Yiu Ming Bonaventure, Chinese University of Hong Kong

Intracerebral hemorrhage (ICH) is a devastating form of acute stroke with poor clinical outcomes. Although ICH accounted only for 28.8% of incident strokes, it was responsible for nearly half of the long-term burden of stroke measured in disability-adjusted life years . In contrast to the improving outcomes seen in ischemic stroke with advances in reperfusion therapy, outcomes of patients with ICH have shown little progress over the past two decades. Current standard care focuses primarily on blood pressure control and supportive management, yet rate of functional independence remained modest. Randomized evidence suggested that fewer than half of the ICH patients achieved independent activities of daily living even with intensive blood pressure lowering.

A cascade of pathophysiological events is thought to determine the prognosis of ICH. First, the mass effect of the hematoma and its expansion with uncontrolled blood pressure cause primary neuronal injury. Second, neuroinflammation involving blood-brain barrier (BBB) dysfunction, activated microglia and astrocytes, together with neutrophil infiltration in response to extravascular blood, propagates neuronal injury, leading to perihematomal edema. Third, the direct neurotoxicity of blood breakdown products and oxidative stress may further amplify neuroinflammation. Mitigating hematoma expansion through intensive blood pressure control therefore only addresses one of these three pathophysiological processes, and is constrained by a short treatment window, mostly within 6 hours. Therapeutic strategies targeting secondary neuroinflammation should therefore be actively pursued. In addition, multimodal studies incorporating longitudinal imaging and omics markers are needed to elucidate the key pathways mediating neuroinflammation following ICH.

Recent preclinical evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RA) may offer neuroprotective benefits in ICH. In animal models of ICH, intracerebroventricular liraglutide suppressed neuroinflammation, prevented brain edema, and reduced neurologic deficits. Previous work from our group has also shown that, across several animal models, GLP-1RA attenuates BBB dysfunction and suppresses neuroinflammatory signaling via microglial modulation. Importantly, a recent translational clinical trial by our team has also provided preliminary evidence that GLP-1RA exerts neuroprotective effects in patients with large vessel occlusion strokes. We therefore hypothesize that compared to standard therapy, administration of GLP-1RA in patients with primary ICH may limit perihaematomal edema, reduce secondary brain injury, and improve neurological outcomes.

In this phase 2, randomized, open-label pilot study with blinded endpoint assessment, we aim to determine the safety and signals for efficacy of GLP-1RA in patients with primary ICH.

Aperçu de l'étude

Statut

Pas encore de recrutement

Les conditions

Intervention / Traitement

Description détaillée

GLP-1RA in Primary Intracerebral Hemorrhage (GLICH) trial is an investigator-initiated, phase 2, multicenter, randomized, open-label trial with blinded endpoint assessment, conducted across centers in Hong Kong Special Administrative Region (HKSAR), Wenzhou and Hefei, China. We aim to recruit 200 patients with primary ICH in the putamen (10-30mL) or thalamus (5-15mL) who present within 24 hours of last-known-well and meet all eligibility criteria. Participants will be randomized in a 1:1 ratio to receive additional semaglutide or just standard therapy after a written informed consent. Patients in the semaglutide group will receive subcutaneous injections of semaglutide on baseline (D0), Day 7 (D7), Day 14 (D14) and Day 21 (D21) after enrollment.

Serial imaging with non-contrast computed tomography (CT) will be performed at baseline, 3+/-1 days, and 7+/-1 days post-enrollment to assess hematoma volume, hematoma expansion, and perihematomal edema (PHE). Brain magnetic resonance imaging (MRI) will be arranged on Day 5-9 (D30) post-ICH to assess the degree of neuronal injury. Blood sampling for omics analysis will be collected at baseline, D3, D7, D14 and D30. Other investigations will be arranged according to clinical requirement. Clinical assessments including National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), Montreal Cognitive Assessment (MoCA) and Mini Mental State Examination (MMSE) will be obtained on D0, Day 90 (D90) and Day 180 (D180). Recruitment targets are 100 patients from Wenzhou, 75 from Hefei and 25 patients from HKSAR according to catchment area size.

Type d'étude

Interventionnel

Inscription (Estimé)

200

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Lieux d'étude

  • Chine
    • Anhui
      • Hefei, Anhui, Chine
        • The First Affiliated Hospital of University of Science and Technology China
        • Contact:
    • Zhejiang
      • Wenzhou, Zhejiang, Chine
        • The First Affiliated Hospital of Wenzhou Medical University
        • Contact:
  • Hong Kong
      • Hong Kong, Hong Kong
        • Chinese University of Hong Kong
        • Contact:

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

  • Adulte
  • Adulte plus âgé

Accepte les volontaires sains

Non

La description

Inclusion Criteria:

  • 1. Primary spontaneous ICH with hematoma location in putamen (10-30mL) or thalamus (5-15mL) on admission CT imaging. Both locations are selected because they are strongly associated with hypertensive arteriopathy-related ICH and there is limited evidence supporting neurosurgical intervention compared with posterior fossa hemorrhages. The thalamic and putaminal volume cutoffs are based on a recent observational study showing that restricting enrolment to 5-15 mL (thalamus) and 10-30 mL (putamen) enriches for patients with substantial but potentially modifiable prognosis while avoiding extremes with ceiling or floor effects. For patients with hematoma involving both putamen and thalamus, a volume cutoff of 5-30mL will be used.
  • 2. National Institutes of Health Stroke Scale (NIHSS) score ≥ 6 AND ≤ 25 at presentation
  • 3. Glasgow Coma Scale (GCS) score ≥ 10
  • 4. Last-known-well (LKW) to presentation time ≤ 24 hours
  • 5. Pre-stroke modified Rankin Scale (mRS) ≤ 2
  • 6. Patients deemed not suitable for acute neurosurgical intervention at the time of randomization
  • 7. Informed consent obtained from patient (if mentally competent) or legal representative, as per national laws, regulations, and applicable ethics committee requirements

Exclusion Criteria:

  • 1. Secondary ICH: ICH due to macrovascular abnormalities (e.g., arteriovenous malformation, aneurysm, arterial dissection, cavernous malformation), coagulopathy, anticoagulant use, antiplatelet overdose, or thrombocytopenia.
  • 2. ICH involving locations other than putamen or thalamus (e.g., lobar, brainstem, cerebellar, isolated intraventricular hemorrhage). Extension of hematoma into other structures is allowed if the hematoma centroid is within the thalamus or putamen, and the hematoma volume does not exist the respective thresholds as stated in Inclusion Criterion 1.
  • 3. ICH with planned neurosurgical procedure prior to randomization, including hematoma evacuation, external ventricular drainage and decompressive craniectomy.
  • 4. Estimated or known body mass index (BMI) < 18 kg/m².
  • 5. Pregnancy, lactation, or positive urine or serum beta human chorionic gonadotropin (β-hCG) test. β-hCG testing should be guided by clinical need.
  • 6. Creatinine clearance < 30 mL/min (estimated by Cockcroft-Gault equation or measured)
  • 7. Severe or fatal comorbid illness with life expectancy < 3 years (e.g., terminal malignancy, advanced organ failure)
  • 8. Participation in another clinical trial investigating a drug, medical device, or medical procedure within 30 days preceding trial inclusion.
  • 9. Known history of allergy or hypersensitivity to GLP-1RA.
  • 10. Family or personal history of multiple endocrine neoplasia (MEN), medullary thyroid carcinoma, or pancreatic carcinoma
  • 11. Active sepsis at time of randomization, defined as a body temperature of ≥ 38.5C, or suspected or documented infection and acute organ dysfunction, operationalized as an increase in SOFA score ≥ 2 points from baseline (baseline assumed 0 if no pre-existing organ dysfunction)
  • 12. Contraindications to proposed imaging studies (e.g., pacemaker incompatibility with MRI where applicable)

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Aucune intervention: Norme de soins
Thérapie médicale standard
Comparateur actif: Semaglutide Group
Patients randomized into the semaglutide group will receive subcutaneous injections of semaglutide on baseline (D0), Day 7 (D7), Day 14 (D14) and Day 21 (D21) after enrollment.
Médicament: Semaglutide, 0.5 mg/mL
0.5mg weekly via subcutaneous injection, a total of 4 injections are given, on Day 0 (D0 day of enrollment, within 24 hours of ICH onset), Day 7 (D7), Day 14 (D14) and Day 21 (D21) after enrollment.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Edema extension distance on Day 7
Délai: Day 7
The perpendicular distance from the hematoma margin to the outermost extent of perihematomal edema on CT imaging.
Day 7

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Proportion of patients with excellent functional outcome (mRS 0-1)
Délai: Day 90±14 and Day 180±14
Modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but remaining able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death)
Day 90±14 and Day 180±14
Proportion of patients with functional independence (mRS 0-2)
Délai: Day 90±14 and Day 180±14
Modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but remaining able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death)
Day 90±14 and Day 180±14
Proportion of patients with ambulatory independence (mRS 0-3)
Délai: Day 90±14 and Day 180±14
Modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but remaining able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death)
Day 90±14 and Day 180±14
Ordinal shift of modified Rankin Scale
Délai: Day 90±14 and Day 180±14
Modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but remaining able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death)
Day 90±14 and Day 180±14
6. Neurological function of participants assessed by National Institute of Health Stroke Scale
Délai: Day 3, Day 7, Day 14, Day 30, Day 90 and Day 180
Zero indicates no stroke symptoms, 1-4 , 5-15, 16-20, 21-42 indicate minor, moderate, moderate to severe, and severe stroke, respectively.
Day 3, Day 7, Day 14, Day 30, Day 90 and Day 180
Hematoma expansion
Délai: Day 3, Day 7
Absolute increase in hematoma volume by ≥ 6mL OR relative increase in hematoma volume by ≥ 33%
Day 3, Day 7
Perihematomal edema volume
Délai: Day 3, Day 7
Volume of edema surrounding the intracerebral hematoma
Day 3, Day 7
Edema extension distance on Day 3
Délai: Day 3
The perpendicular distance from the hematoma margin to the outermost extent of perihematomal edema on CT imaging.
Day 3
Need for acute neurosurgical intervention
Délai: Day 180
Any neurosurgical intervention performed as a result of neurological or radiological deterioration.
Day 180

Autres mesures de résultats

Mesure des résultats
Description de la mesure
Délai
Cognitive function by Montreal Cognitive Assessment
Délai: Day 90, Day 180
26 - 30: Normal cognitive function; 18 - 25: Mild Cognitive Impairment (MCI) 10 - 17: Moderate Cognitive Impairment / Dementia; ≤ 9: Severe Impairment
Day 90, Day 180
Cognitive function by Mini Mental State Examination
Délai: Day 90, Day 180
24-30: Normal Cognition (no impairment); 19-23: Mild Cognitive Impairment 10-18: Moderate Cognitive Impairment; ≤9: Severe Cognitive Impairment
Day 90, Day 180
Post ICH seizure or epilepsy
Délai: Day 180
Post ICH seizure is defined as any seizure that after the ICH event. Post ICH epilepsy is defined as unprovoked seizures 7 days after the ICH event.
Day 180

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Chinese University of Hong Kong

Collaborateurs

First Affiliated Hospital of Wenzhou Medical University
The First Affiliated Hospital of University of Science and Technology China

Les enquêteurs

  • Chercheur principal: Bonaventure Yiu Ming IP, MB ChB,PhD, Chinese University of Hong Kong
  • Chercheur principal: Wei HU, MD, The First Affiliated Hospital of University of Science and Technology China
  • Chercheur principal: Xinshi WANG, MD, First Affiliated Hospital of Wenzhou Medical University

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Estimé)

15 juin 2026

Achèvement primaire (Estimé)

14 juin 2028

Achèvement de l'étude (Estimé)

31 décembre 2028

Dates d'inscription aux études

Première soumission

22 mai 2026

Première soumission répondant aux critères de contrôle qualité

22 mai 2026

Première publication (Réel)

29 mai 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

29 mai 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

22 mai 2026

Dernière vérification

1 mai 2026

Plus d'information

Termes liés à cette étude

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • CREC 2026.169

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

NON

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Oui

Étudie un produit d'appareil réglementé par la FDA américaine

Non

produit fabriqué et exporté des États-Unis.

Oui

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