The Galcanezumab AD trial (NCT07323927) is an investigator-initiated Phase 1 clinical study evaluating the efficacy and safety of galcanezumab, a monoclonal antibody targeting calcitonin gene-related peptide (CGRP), in patients with mild-to-moderate Alzheimer's disease. This trial is conducted by Xuanwu Hospital, Capital Medical University in Beijing, China[1].
Galcanezumab (brand name Emgality) is already approved for migraine prevention. This trial explores whether CGRP modulation may provide cognitive benefits in Alzheimer's disease, based on emerging evidence that CGRP plays complex roles in both neuroprotection and pathological processes in the brain.
Trial Identifier: NCT07323927
Status: Recruiting (as of March 2026)
Start Date: August 2025
Estimated Completion: March 2027
Phase: Early Phase 1
Enrollment: 10 participants
Sponsor: Xuanwu Hospital, Capital Medical University
Calcitonin gene-related peptide (CGRP) is a neuropeptide with complex, sometimes paradoxical effects in the nervous system. While initially studied in the context of migraine pathophysiology, emerging research suggests CGRP may play important roles in both normal cognitive function and neurodegenerative processes[2][3]:
Potential Protective Effects:
Potential Pathological Effects:
This duality makes CGRP an intriguing therapeutic target. The hypothesis is that modulation (rather than complete blockade) may restore optimal CGRP signaling in AD patients[4].
Epidemiological studies have revealed interesting associations between migraine and Alzheimer's disease:
This investigator-initiated trial aims to directly test whether CGRP modulation with galcanezumab can improve cognitive outcomes in AD.
Design: Single-arm, open-label, Phase 1 clinical trial
Allocation: All participants receive galcanezumab (no placebo control)
Duration: 24 weeks of treatment with 12-week follow-up (36 weeks total)
| Phase | Dose | Administration |
|---|---|---|
| Loading | 240 mg | Single subcutaneous injection at baseline |
| Maintenance | 120 mg | Every 4 weeks (weeks 4, 8, 12, 16, 20, 24) |
Total: 6 doses over 24 weeks
| Visit | Timepoint | Assessments |
|---|---|---|
| Visit 1 (Screening) | Week -4 to 0 | Eligibility verification, baseline cognitive testing |
| Visit 2 (Baseline) | Week 0 | Pre-treatment assessments, first dose administration |
| Visit 3 | Week 12 | Mid-treatment cognitive assessment |
| Visit 4 | Week 24 | End-of-treatment assessment |
| Visit 5 | Week 36 | 12-week post-treatment follow-up |
CGRP Levels in Cerebrospinal Fluid and Plasma
Cognitive Measures:
Functional Measures:
Safety Measures:
This pilot study represents an exploratory investigation into CGRP modulation as a potential AD therapeutic approach. While the sample size is small (n=10), the comprehensive biomarker and imaging assessments may provide valuable mechanistic insights:
Results from this trial may inform future Phase 2/3 studies if positive signals are observed.
Galcanezumab AD - NCT07323927. 2026. ↩︎
Wu L, Chen X, Liu Y, et al. Calcitonin gene-related peptide in Alzheimer's disease - emerging role and therapeutic potential. Front Aging Neurosci. 2023. ↩︎
Recober A, Russo AF. Calcitonin gene-related peptide and migraine: continuing the quest. Headache. 2023. ↩︎
Wang Q, Liang X, Wang L. CGRP-mediated signaling in cognitive impairment and neuroprotection. J Alzheimers Dis. 2022. ↩︎
Rodrigues MR, Martins IO, Targa Y, et al. Migraine and Alzheimer's disease - a bidirectional relationship?. J Alzheimers Dis. 2023. ↩︎