Table 2.
Ongoing stem cell trials in humans with Alzheimer’s disease
| Trial ID | NCT01547689 | NCT02054208 | NCT02600130 | NCT02912169 | NCT02833792 | NCT02672306 | NCT02899091 |
|---|---|---|---|---|---|---|---|
| Date | 03/2012 to 12/2016 | 02/2014 to 02/2018 | 11/2015 to 10/2019 | 11/2015 to 12/2017 | 06/2016 to 06/2018 | 05/2016 to 10/2019 | 09/2016 to 06/2018 |
| Study design | Phase I/II Safety and efficacy Intervention Single group open-label |
Phase I/II Safety and efficacy Intervention Randomized Double-blind Placebo-controlled |
Phase I Safety and efficacy Intervention Randomized Double-blind Placebo-controlled |
Phase I/II Safety and efficacy Intervention Non-randomized Single group Open-label Multi-centre |
Phase II Safety and efficacy Intervention Randomized Single-blind Placebo-controlled Multi-centre |
Phase I/II Safety and efficacy Intervention Randomized Double-blind Placebo-controlled |
Phase I/II Safety and efficacy Intervention Randomized Double-blind Placebo-controlled |
| Stage | Active | Recruiting | Recruiting | Recruiting | Recruiting | Not yet recruiting | Not yet recruiting |
| Cell type | hUCB-MSCs | hUCB-MSCs | hBM-MSCs | hAD-SVF | hBM-MSCs | hUCB-MSCs | hPD-MSCs |
| Inclusion criteria | Age 50–85 Probable AD K-MMSE 3–20 |
Age 50–85 Probable AD K-MMSE 18–26 Amyloid+ PIB/florbetaben-PET |
Age 50–80 Diagnosed AD K-MMSE 18–24 Amyloid+ PET |
Age ≥55 Probable AD (NINCDS-ADRDA and DSM IV) |
Age 55–80 Mild-moderate AD K-MMSE 12–24 Amyloid+ florbetapir-PET |
Age 50–85 Probable AD K-MMSE 3–20 |
Age ≥50 Probable AD K-MMSE 10–26 Amyloid+ PET |
| Delivery route | Intravenous infusion | Ommaya Reservoir intraventricular injection | Intravenous infusion | Intravenous and intranasal infusion | Intravenous infusion | Intravenous infusion | Intravenous infusion |
| Arms |
n = 30 Eight infusions once every 2 weeks in the first month of each quarter 2 × 107 cells per infusion |
n = 42 Three injections at 4-week intervals Low-dose group: 1 × 107 cells per injection High-dose group: 3 × 107 cells per injection Placebo group: saline |
n = 30 Single infusion Low-dose group: 2 × 107 cells High-dose group: 1 × 108 cells Placebo group: Plasmalyte A and 1% human serum albumin |
n = 100 Single intravenous infusion or intravenous and intranasal infusion |
n = 40 Single infusion Crossover at 6 months post-infusion Group 1: 1.5 × 106 cells/kg bodyweight Group 2: lactated Ringer’s Solution |
n = 40 Eight infusions at 2-week intervals Treatment group: 2 × 107 cells per infusion Placebo group: saline |
n = 24 Single or repeat (day 0 and week 4) infusions Arm 1: K-MMSE 20–26 Arm 2: K-MMSE 10–19 Group1: 2 × 108 cells Group 2: two infusions of 2 × 108 cells Placebo group: placebo infusion |
| Outcome measures |
10 weeks FU
No. of adverse events Change from baseline: ADAS-cog, MMSE, CIBIC, ADCS-ADL and CGA-NPI CSF transthyretin, Aβ and tau Blood Thl/Th2 cytokines |
24 weeks FU
No. of adverse events Change from baseline: ADAS-cog, S-IADL, K-MMSE, CIBIC, CGA-NPI and CDR CSF biomarkers MRI DTI mapping, PIB-PET and FDG-PET |
30 days FU
No. of adverse events 2, 4, 13, 39, and 52 weeks FU Change from baseline: ADAS-cog, MMSE, CGA-NPI and GDS CSF inflammatory markers, Aβ and tau Blood inflammatory and AD biomarkers MRI brain volumetry |
12 months FU
No. of adverse events 3 and 6 months FU Change from baseline: FAQ, GDS, MMSE and ADCS-ADL |
18 months FU
No. of adverse events Change from baseline: Neurological examinations |
10 weeks FU
No. of adverse events Change from baseline: ADAS-cog, MMSE, ADCS-CCGIC, ADCS-ADL and CGA-NPI CSF Aβ and tau Blood Aβ |
48 weeks FU
No. of adverse events Change from baseline: ADAS-cog, K-MMSE, GDS, CDR, K-IADL, CGA-NPI, CIBIC and SF-36 CSF Aβ and tau Brain MRI, amyloid-PET, FDG-PET, CMRglc Quantitative ECG |
Aβ amyloid beta, AD Alzheimer’s disease, ADAS-cog Alzheimer’s Disease Assessment Scale-Cognitive Subscale, ADCS-ADL Alzheimer’s Disease Cooperative Study Activities of Daily Living, ADCS-CCGIC Alzheimer’s Disease Cooperative Study Clinician’s Global Impression of Change, CDR Clinical Dementia Rating, CGA-NPI Caregiver-administered Neuropsychiatric Inventory, CIBIC Clinician’s Interview-Based Impression of Change, CMRglc cerebral metabolic rate for glucose, CSF cerebrospinal fluid, DSM Diagnostic and Statistical Manual of Mental Disorders, DTI diffusion tensor imaging, ECG electrocardiogram, FAQ Functional Activities Questionnaire, FDG fluorodeoxyglucose, FU follow-up, GDS Geriatric Depression Scale, hAD-SVF human adipose-derived stromal vascular fraction, hBM-MSC human bone marrow-derived mesenchymal stem cell, hPD-MSC human placenta-derived mesenchymal stem cell, hUCB-MSC human umbilical cord blood-derived mesenchymal stem cell, K-IADL Korean Instrumental Activities of Daily Living, K-MMSE Korean version of Mini-Mental State Evaluation, MMSE Mini-Mental State Evaluation, MRI magnetic resonance imaging, NINCDS-ADRDA National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association, PET positron emission tomography, PIB Pittsburgh compound B, SF-36 36-item Short Form Health Survey, S-IADL Seoul-Instrumental Activities of Daily Living, Th T helper