TABLE 1.
Characteristics of trials of insulin for the treatment of Alzheimer's disease
| Trial number | Agent | Date registered | Trial status | Trial phase | Enrolment | MMSE range | Treatment duration | Primary clinical outcomes | Outcome biomarkers |
|---|---|---|---|---|---|---|---|---|---|
| NCT00581867 | Insulin aspart | 12/19/07 | Completed |
Phase 1 Phase 2 |
31 | Single dose | fMRI measure of hippocampal activation | ||
| NCT02503501 | Insulin glulisine | 7/14/15 | Terminated | Phase 2 | 49 | MoCA 18–27 | 26 weeks |
ADAS‐cog13 CDR |
CSF Aβ 42 CSF tau CSF phosphotau cerebral glucose metabolism via FDG PET |
| NCT01145482 | Insulin aspart | 6/15/10 | Completed | Not applicable | 12 | >15 | 2 doses | Cerebral glutamate concentration | |
| NCT02462161 | Insulin aspart | 6/1/15 | Completed | Phase 1 | 24 | 12 weeks |
ADAS‐cog MCI scores |
CSF Aβ CSF tau Plasma Aβ Plasma tau Cortical thickness in AD‐vulnerable regions Inflammatory markers |
|
| NCT01636596 | Insulin lispro | 7/6/12 | Withdrawn | Not applicable | 0 | ≥15 | 26 weeks |
MMSE CDT |
Cerebral glucose metabolism via FDG PET Basal metabolism |
| NCT01436045 | Insulin glulisine | 9/16/11 | Completed | Phase 2 | 12 | 18–26 | Single dose |
Trails B ‐ seconds Trails B ‐ errors Cognitive performance via RBANS |
|
| NCT01767909 | Insulin regular (Humulin R) | 1/10/13 | Completed |
Phase 2 Phase 3 |
240 | ≥20 | 26 weeks | ADAS‐cog12 |
CSF Aβ CSF tau Degree of hippocampal/entorhinal atrophy |
| NCT01595646 | Insulin detemir | 5/8/12 | Completed | Phase 2 | 37 | 16 weeks | Verbal memory composite (delayed story recall and Buschke selective reminding test) |
CSF Aβ CSF tau CSF TTau‐P181/Aβ 42 ratio Plasma Aβ Plasma tau Cerebral blood flow via MRI OGTT |
|
| NCT01547169 | Insulin detemir | 2/7/12 | Completed | Phase 2 | 60 | 3 weeks | Verbal memory composite (immediate + delayed story recall and immediate + delayed list recall) |
Plasma Aβ Plasma tau OGTT |
|
| NCT00438568 | Insulin regular (Novolin R) | 7/21/2007 | Completed | Phase 2 | 173 | 16 weeks | Changes in cognition |
CSF Aβ Plasma Aβ Cerebral glucose metabolism via PET |
Abbreviations: Aβ, amyloid beta; ADAS‐cog, Alzheimer's Disease Assessment Scale ‐ Cognitive Subscale; CSF, cerebrospinal fluid; CT, computed tomography; FDG PET, fluorodeoxyglucose positron emission tomography; GDS, Global Deterioration Scale; MCI, mild cognitive impairment; MMSE, Mini‐Mental State Exam; MRI, magnetic resonance imaging; MoCA, Montreal Cognitive Assessment; OGTT, Oral Glucose Tolerance Test; RBANS, Repeatable Battery for the Assessment of Neuropsychological Status.