Mild Cognitive ImpairmentPhase 1AlloNCT02221622
Allopregnanolone for Mild Cognitive Impairment Due to Alzheimer's Disease or Mild AD
A Phase 1 study testing Allopregnanolone injection (intravenous solution) in people with Mild Cognitive Impairment and Alzheimer Disease, run by University of Southern California at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the safety and tolerability of allopregnanolone, a naturally occurring brain steroid, in mild cognitive impairment and early Alzheimer's disease participants. The primary goal is to determine the maximally tolerated dose. Read more about this study
- Who is it for?
- Ages 55 years and older
- Conditions the study is for
- Mild Cognitive Impairment, Alzheimer Disease
- What is being tested?
- Allopregnanolone injection (intravenous solution)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2014to Feb 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men or postmenopausal women
- 55 years of age or older
- Diagnosis of MCI due to AD or mild AD
- MMSE > 20 at screen
- Capacity to provide informed consent
- Residing in the community with a caregiver able to accompany the patient to clinic visits
- No medical contraindications to participation
- Willingness to comply with study procedures
Who cannot join
- Use of benzodiazepines, sedative/hypnotics, anticonvulsants, antipsychotics, and other drugs that might interact with the GABA-A receptor complex
- Seizure disorder, history of stroke, focal brain lesion, traumatic brain injury, substance abuse, malignancy
- Clinically significant laboratory or ECG abnormality
- MRI indicative of any other significant abnormality, including but not limited to evidence of a cerebral contusion, encephalomalacia, aneurysms, vascular malformations, subdural hematoma, or space occupying lesions
- Any condition that would contraindicate an MRI such as the presence of metallic objects in the eyes, skin, heart, or body
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Southern California - Alzheimer Disease Research Center - Healthcare Consultation Center II
Los Angeles, California, 90033
About this study
Official title: Allopregnanolone Regenerative Therapeutic for MCI/AD: Dose Finding Phase 1
The purpose of this study is to evaluate the safety and tolerability of allopregnanolone, a naturally occurring brain steroid, in mild cognitive impairment and early Alzheimer's disease participants. The primary goal is to determine the maximally tolerated dose.
Read the detailed description
- Each dose group will be comprised of 8 participants (6 randomized to allopregnanolone; 2 randomized to placebo) administered one dose of allopregnanolone or placebo once per week for 12 weeks. A higher dose will be administered to the next group of participants when the lower dose is shown to be safe and tolerable. 2) Pharmacokinetic analyses will be conducted on blood samples taken from participants at the beginning and end of the trial. 3) The trial will assess safety including via MRI brain imaging.
- Conditions
- Mild Cognitive Impairment, Alzheimer Disease
- Being tested
- Allopregnanolone injection (intravenous solution), Placebo injection (intravenous solution)
- Keywords
- Alzheimer's disease, Mild Cognitive Impairment, Dementia, Regenerative therapeutic
- Medical subject headings
- Cognitive Dysfunction, Alzheimer Disease, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allopregnanolone injection (intravenous solution)Drug
Also called 3α,5α-tetrahydroprogesterone, 3α-hydroxy-5α-pregnan-20-one
Allopregnanolone intravenous infusion
Placebo injection (intravenous solution)Drug
Placebo intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| Allopregnanolone 2 mg | Experimental | Drug: Allopregnanolone injection (intravenous solution) once per week for 12 weeks Receives: Drug: Allopregnanolone injection (intravenous solution) |
| Allopregnanolone 4 mg | Experimental | Drug: Allopregnanolone injection (intravenous solution) once per week for 12 weeks Receives: Drug: Allopregnanolone injection (intravenous solution) |
| Allopregnanolone 6-18 mg | Experimental | Drug: Allopregnanolone injection (intravenous solution) once per week for 12 weeks Receives: Drug: Allopregnanolone injection (intravenous solution) |
| Placebo | Placebo comparator | Drug: Placebo injection (intravenous solution) once per week for 12 weeks Receives: Drug: Placebo injection (intravenous solution) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety profile: Adverse events
Incidence and severity of treatment emergent adverse events assessed weekly per treatment arm.
Measured: From Baseline to week 16
Safety profile: Clinical laboratory measurements
Evaluating the proportion of subjects exceeding pre-established critical values per treatment arm:
Alanine aminotransferase (ALT, U/L) > 5 times upper normal limit Aspartate aminotransferase (AST, U/L) > 5 times upper normal limit Total serum bilirubin (mg/dl) > 2 times upper normal limit Serum creatinine (mg/dl) > 2 times upper normal limit Serum creatine phosphokinase (U/L) > 5 times upper normal limit
Measured: From Baseline to week 13
Safety profile: ARIA
MRI based assessment of amyloid related imaging abnormalities (ARIA); proportion of subjects with ARIA
Measured: From Baseline to week 13
Safety profile: Physical and neurological examination
To evaluate the proportion of abnormal examination findings of subjects in each treatment arm.
Measured: From Baseline to week 16
Tolerability - Maximum tolerated dose (MTD)
Onset of sedation will define the upper most limit of drug dose
Measured: From Baseline to week 12
Secondary outcomes (7)
Pharmacokinetic profile after single and multiple doses: Maximum Concentration (Cmax)
Measurement of maximum concentration
Measured: Weeks: 1 and 12
Pharmacokinetic profile after single and multiple doses: time attain to Cmax (Tmax)
Time to attain maximum concentration.
Measured: Weeks: 1 and 12
Pharmacokinetic profile after single and multiple doses: Area under the curve (AUC)
Pharmacokinetic parameter.
Measured: Weeks: 1 and 12
Pharmacokinetic profile after single and multiple doses: Drug Clearance (CL)
Pharmacokinetic parameter.
Measured: Weeks: 1 and 12
Pharmacokinetic profile after single and multiple doses: apparent volume of distribution at steady state (Vss)
Pharmacokinetic parameter.
Measured: Weeks: 1 and 12
Cognitive tests (ADAS-Cog; MMSE/MoCA; ADCS-CGIC; CogState)
Alzheimer's disease Assessment Scale Cognitive Subscale 14 (ADAS-Cog); Mini-Mental State Exam (MMSE); Montreal Cognitive Assessment (MoCA); Alzheimer's disease Cooperative Study Clinical Global Impression of Change (ADCS-CGIC); CogState 12-min battery (CogState)
Measured: Baseline to Week 13
Brain MRI volumetrics
Gray matter, white matter and hippocampal volume measurements, including subfield analysis.
Measured: Baseline and Week 13
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2014 (estimated)
- Study startAug 2014
- Primary completionFeb 2018
- Study completionFeb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- More trials run by University of Southern CaliforniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Southern California
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Roberta D Brinton, Ph.D., Principal investigator, University of Southern CaliforniaLon S Schneider, M.D., Principal investigator, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02221622
- Sponsor's protocol ID
- AlloPhase1
- Other IDs
- 1UF1AG046148
- Acronym
- Allo
- Status last verified
- May 2018
- First submitted
- 2 Jul 2014
- Last updated
- 5 Jul 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 33344752
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Allopregnanolone Regenerative Therapeutic for MCI/AD: Dose Finding Phase 1
- ClinicalTrials.gov ID
- NCT02221622
- Acronym / sponsor ID
- Allo / AlloPhase1
- Conditions
- Mild Cognitive Impairment, Alzheimer Disease
- Keywords
- Alzheimer's disease, Mild Cognitive Impairment, Dementia, Regenerative therapeutic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University of Southern CaliforniaUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- Aug 2014
- Primary completion
- Feb 2018 (actual)
- Study completion
- Feb 2018 (actual)
- First posted
- 20 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety and tolerability of allopregnanolone, a naturally occurring brain steroid, in mild cognitive impairment and early Alzheimer's disease participants. The primary goal is to determine the maximally tolerated dose.
Detailed description
- Each dose group will be comprised of 8 participants (6 randomized to allopregnanolone; 2 randomized to placebo) administered one dose of allopregnanolone or placebo once per week for 12 weeks. A higher dose will be administered to the next group of participants when the lower dose is shown to be safe and tolerable. 2) Pharmacokinetic analyses will be conducted on blood samples taken from participants at the beginning and end of the trial. 3) The trial will assess safety including via MRI brain imaging.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Allopregnanolone 2 mg | Experimental | Drug: Allopregnanolone injection (intravenous solution)Drug: Allopregnanolone injection (intravenous solution) once per week for 12 weeks |
| Allopregnanolone 4 mg | Experimental | Drug: Allopregnanolone injection (intravenous solution)Drug: Allopregnanolone injection (intravenous solution) once per week for 12 weeks |
| Allopregnanolone 6-18 mg | Experimental | Drug: Allopregnanolone injection (intravenous solution)Drug: Allopregnanolone injection (intravenous solution) once per week for 12 weeks |
| Placebo | Placebo comparator | Drug: Placebo injection (intravenous solution)Drug: Placebo injection (intravenous solution) once per week for 12 weeks |
Who may qualify
- Ages
- 55 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Men or postmenopausal women
- 55 years of age or older
- Diagnosis of MCI due to AD or mild AD
- MMSE > 20 at screen
- Capacity to provide informed consent
Key exclusion criteria (5 listed)
- Use of benzodiazepines, sedative/hypnotics, anticonvulsants, antipsychotics, and other drugs that might interact with the GABA-A receptor complex
- Seizure disorder, history of stroke, focal brain lesion, traumatic brain injury, substance abuse, malignancy
- Clinically significant laboratory or ECG abnormality
- MRI indicative of any other significant abnormality, including but not limited to evidence of a cerebral contusion, encephalomalacia, aneurysms, vascular malformations, subdural hematoma, or space occupying lesions
- Any condition that would contraindicate an MRI such as the presence of metallic objects in the eyes, skin, heart, or body
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Allopregnanolone injection (intravenous solution)Also: 3α,5α-tetrahydroprogesterone, 3α-hydroxy-5α-pregnan-20-oneAllopregnanolone intravenous infusion | Drug | Allopregnanolone 2 mg, Allopregnanolone 4 mg, Allopregnanolone 6-18 mg |
| Placebo injection (intravenous solution)Placebo intravenous infusion | Drug | Placebo |
Primary outcome
Safety profile: Adverse events
Time frame: From Baseline to week 16
Incidence and severity of treatment emergent adverse events assessed weekly per treatment arm.
Safety profile: Clinical laboratory measurements
Time frame: From Baseline to week 13
Evaluating the proportion of subjects exceeding pre-established critical values per treatment arm: Alanine aminotransferase (ALT, U/L) > 5 times upper normal limit Aspartate aminotransferase (AST, U/L) > 5 times upper normal limit Total serum bilirubin (mg/dl) > 2 times upper normal limit Serum creatinine (mg/dl) > 2 times upper normal limit Serum creatine phosphokinase (U/L) > 5 times upper normal limit
Safety profile: ARIA
Time frame: From Baseline to week 13
MRI based assessment of amyloid related imaging abnormalities (ARIA); proportion of subjects with ARIA
Safety profile: Physical and neurological examination
Time frame: From Baseline to week 16
To evaluate the proportion of abnormal examination findings of subjects in each treatment arm.
Tolerability - Maximum tolerated dose (MTD)
Time frame: From Baseline to week 12
Onset of sedation will define the upper most limit of drug dose
7 secondary outcomes
Pharmacokinetic profile after single and multiple doses: Maximum Concentration (Cmax)
Time frame: Weeks: 1 and 12
Pharmacokinetic profile after single and multiple doses: time attain to Cmax (Tmax)
Time frame: Weeks: 1 and 12
Pharmacokinetic profile after single and multiple doses: Area under the curve (AUC)
Time frame: Weeks: 1 and 12
Pharmacokinetic profile after single and multiple doses: Drug Clearance (CL)
Time frame: Weeks: 1 and 12
Pharmacokinetic profile after single and multiple doses: apparent volume of distribution at steady state (Vss)
Time frame: Weeks: 1 and 12
Cognitive tests (ADAS-Cog; MMSE/MoCA; ADCS-CGIC; CogState)
Time frame: Baseline to Week 13
Brain MRI volumetrics
Time frame: Baseline and Week 13
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2019.
- Derived from this study: PubMed 33344752Hernandez 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roberta D Brinton, Ph.D. principal investigator
University of Southern California
Lon S Schneider, M.D. principal investigator
University of Southern California
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Allopregnanolone injection (intravenous solution) in people with Mild Cognitive Impairment and Alzheimer Disease, run by University of Southern California at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety profile: Adverse events (time frame: From Baseline to week 16). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02221622, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jul 2019.