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| ID | Type | Description | Link |
|---|---|---|---|
| R01AG063826 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
| Syneos Health | OTHER |
| University of Southern California | OTHER |
| ADM Diagnostics |
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A phase 2, double-blind, randomized, placebo-controlled clinical trial to evaluate the safety and efficacy of Allopregnanolone as a regenerative therapeutic for Alzheimer's disease.
This is a proof-of-concept phase 2 clinical trial to investigate the long-term safety and efficacy of Allo to function as a regenerative therapeutic to restore structural integrity and cognitive function of the brain in participants with mild Alzheimer's disease (AD) dementia. Study participants will be male and female, diagnosed with probable AD, Mini-Mental State Exam (MMSE) 20 to 26, ages 55 to 80 years old.
After a 2-4-week screening period, participants will be randomized to 4 mg Allo (administered intravenously over 30 minutes, once per week, in clinic) or matching placebo, 1:1 allocation, for a period of 6 months. After 6 months, all participants in the placebo group will be crossed-over to receive Allo for the remainder of the study (3 month open-label phase). Brain imaging to evaluate the primary endpoint will be conducted at baseline, 3 and 6 months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Allo group | Experimental | Allopregnanolone 4mg IV 30-minute infusion once per week for 6 months. |
|
| Control group | Placebo Comparator | Placebo (normal saline) IV 30-minute infusion once per week for 6 months. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Allopregnanolone | Drug | Allopregnanolone 4mg IV via 30-minute infusion, once per week. |
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| Measure | Description | Time Frame |
|---|---|---|
| Hippocampal volume | mm3 | Baseline to 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Cambridge Cognition's Paired Associates Learning Test | Total errors score (adjusted) - number of errors made by the participant (range: 0 to ~120). Higher scores indicate poor performance. | Baseline to 6 months |
| Cambridge Neuropsychological Test Automated Battery (CANTAB) |
| Measure | Description | Time Frame |
|---|---|---|
| Other regional brain volumes | Change in regional brain volumes (mm3) | Baseline to 6 and 9 months |
| Diffusion tensor imaging (DTI) | Change in white matter tract diffusion (scalar values and/or mm2/sec) |
Main Inclusion Criteria:
Main Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Roberta D Brinton, PhD | University of Arizona | Principal Investigator |
| Lon Schneider, MD | University of Southern California | Principal Investigator |
| Gerson D Hernandez, MD, MPH | University of Arizona | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Perseverance Research Center | Scottsdale | Arizona | 85253 | United States | ||
| University of Arizona / Clinical & Translational Sciences Research Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35310526 | Background | Raikes AC, Hernandez GD, Matthews DC, Lukic AS, Law M, Shi Y, Schneider LS, Brinton RD. Exploratory imaging outcomes of a phase 1b/2a clinical trial of allopregnanolone as a regenerative therapeutic for Alzheimer's disease: Structural effects and functional connectivity outcomes. Alzheimers Dement (N Y). 2022 Mar 14;8(1):e12258. doi: 10.1002/trc2.12258. eCollection 2022. | |
| 33344752 | Background | Hernandez GD, Solinsky CM, Mack WJ, Kono N, Rodgers KE, Wu CY, Mollo AR, Lopez CM, Pawluczyk S, Bauer G, Matthews D, Shi Y, Law M, Rogawski MA, Schneider LS, Brinton RD. Safety, tolerability, and pharmacokinetics of allopregnanolone as a regenerative therapeutic for Alzheimer's disease: A single and multiple ascending dose phase 1b/2a clinical trial. Alzheimers Dement (N Y). 2020 Dec 16;6(1):e12107. doi: 10.1002/trc2.12107. eCollection 2020. |
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| UNKNOWN |
Participants are assigned to the active intervention or placebo in parallel for 12 months. After 12 months, all participants in the placebo group will be crossed-over to receive Allo for the remainder of the study (6 month open-label phase).
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After 6 months participants and study personnel will be aware of the open label phase, but initial randomization will remain blind during the entire length of the study (placebo-controlled and open-label periods); that is, all participants and study personnel are blinded to each participant's randomization to initial treatment group.
| Placebo | Other | Normal saline solution IV via 30-minute infusion, once per week |
|
Composite score (higher score indicate better outcome) |
| Baseline to 6 months |
| Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) 11 | Total score (range 0 to 70); higher scores indicate poor performance. | Baseline to 6 months |
| Alzheimer's Disease Cooperative Study (ADCS) Instrumental Activities of Daily (iADL) Living (iADL) | iADL subscore (range 0-56): Lower score indicates greater severity | Baseline to 6 months |
| Safety and tolerability | Frequency of adverse events and serious adverse events | Baseline to 6 months |
| Baseline to 6 and 9 months |
| Resting state functional MRI | Change in functional connectivity (z transformed correlations) | Baseline to 6 and 9 months |
| Arterial spin labeling (ASL) | Change in regional cerebral blood flow (mL/100g) | Baseline to 6 and 9 months |
| Exploratory blood based biomarkers | Change from baseline in biomarkers of AD pathology, neurogenesis and inflammation | Baseline to 6 and 9 months |
| Clinical Dementia Rating (CDR) | Sum of boxes score (CDR-SB): range 0-18 | Baseline to 6 and 9 months |
| Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) 14 | Total score (range 0-90) | Baseline to 6 and 9 months |
| Mini Mental State Examination (MMSE) | Total score (range 0-30) | Baseline to 6 and 9 months |
| Neuropsychiatric Inventory-Questionnaire (NPI-Q) | Total score (range 0-36). Higher scores indicate greater symptom severity | Baseline to 6 and 9 months |
| EuroQol 5-Dimension / 5-Level health-related quality of life scale scores (EQ-5D-5L) | Reported as frequency, percentage and index value. | Baseline to 6 and 9 months |
| Quality of Life in Alzheimer's Disease scale (QoL-AD) | Total score (range 13-52). Higher score indicate better QoL | Baseline to 6 and 9 months |
| Zarit Burden Interview (ZBI) | Total score (range 0-48). Higher scores indicate high burden | Baseline to 6 and 9 months |
| Tucson |
| Arizona |
| 85721 |
| United States |
| ATP Clinical Research | Costa Mesa | California | 92626 | United States |
| Syrentis Clinical Research | Santa Ana | California | 92705 | United States |
| Optimus U Corporation | Miami | Florida | 33135 | United States |
| Miami Jewish Health | Miami | Florida | 33137 | United States |
| Combined Research Orlando | Orlando | Florida | 32807 | United States |
| Conquest Research | Winter Park | Florida | 32789 | United States |
| MedVadis Research | Waltham | Massachusetts | 02451 | United States |
| 23438839 | Background | Brinton RD. Neurosteroids as regenerative agents in the brain: therapeutic implications. Nat Rev Endocrinol. 2013 Apr;9(4):241-50. doi: 10.1038/nrendo.2013.31. Epub 2013 Feb 26. |
| 16842093 | Background | Brinton RD, Wang JM. Therapeutic potential of neurogenesis for prevention and recovery from Alzheimer's disease: allopregnanolone as a proof of concept neurogenic agent. Curr Alzheimer Res. 2006 Jul;3(3):185-90. doi: 10.2174/156720506777632817. |
| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| D019636 | Neurodegenerative Diseases |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D011280 | Pregnanolone |
| ID | Term |
|---|---|
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
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