Alzheimer DiseaseENERGISENCT06372587
Next-Generation alzheImer'S Therapeutics
A study testing genetically encoded engineered proteins in people with Alzheimer Disease, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
Trial summary
Is this the right time to use next-generation approaches in Alzheimer's disease (AD)? In recent years, several large clinical trials testing treatments for AD have failed, putting the entire field on a reset. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- genetically encoded engineered proteins
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 1 siteItaly
- Study dates
- 19 Dec 2023to 28 Feb 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Manifest clinical criteria for probable AD;
- Age between 18 and 80 years;
- Signed informed consent obtained;
Who cannot join
- Patients suffering from other neurological diseases;
- Patients with coagulation disorders or in treatment with anticoagulant drugs;
- Patients suffering from dermatological diseases and connective tissue diseases;
- Patients suffering from other organic, psychiatric diseases or laboratory abnormalities could preclude participation or invalidate the study results;
- Inability to give informed consent.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Fondazione Policlinico Universitario A. Gemelli IRCCS
Roma, 00168
CRISTIAN RIPOLI, +390630154966, cristian.ripoli@policlinicogemelli.it
CRISTIAN RIPOLI
About this study
Official title: Leveraging Genetically Encoded engiNeered protEins foR Next-Generation alzheImer'S Therapeutics
Is this the right time to use next-generation approaches in Alzheimer's disease (AD)? In recent years, several large clinical trials testing treatments for AD have failed, putting the entire field on a reset. AD drug trials have almost exclusively sought to use antibodies targeted toward misfolded amyloid and tau proteins. Of note, although these approaches have failed, they were designed to cover both familial and sporadic forms of AD. On the other hand, the failure in developing new effective drugs is attributed to, but not limited to, the highly heterogeneous nature of AD with multiple underlying hypotheses and multifactorial pathology. The idea underlying this project is based on the assumption that learning and memory disorders can arise when the connections between neurons do not change appropriately in response to experience. Thus, by intervening on the core mechanisms of the cellular correlate of learning and memory, i.e., synaptic plasticity, the investigators expect to preserve some of the essential brain functions in AD. By overcoming the limits of traditional AD therapeutic approaches, the investigators will use genetically encoded engineered proteins (GEEPs), which the investigators developed and tested in vitro and in murine models, to control their activity in living human neurons boosting synaptic plasticity. Indeed, outstanding and relevant progress in understanding synaptic physiology empowers the possibility to prevent or limit brain disease like never before. The investigators designed GEEPs to address some of the leading causes of synaptic plasticity failures documented in AD. Thus, GEEPs will be tested in human induced pluripotent stem cells (hiPSCs)-derived living neurons obtained from reprogrammed peripheral tissues of participants with Alzheimer's diseases. hiPSCs will be obtained from fibroblast-derived from a skin biopsy of participants with AD and controls performed in local anesthesia using a 4 mm punch. The findings will provide the first preclinical study on the effect of genetically engineered proteins to control essential pathways implicated in synaptic plasticity on AD-related cognitive decline.
- Conditions
- Alzheimer Disease
- Being tested
- genetically encoded engineered proteins
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
genetically encoded engineered proteinsOther
using genetically encoded engineered proteins to obtain an inducible control of their activity in living human neurons promoting synaptic plasticity and/or preventing dendritic spines loss
| Study group | Role | What they receive |
|---|---|---|
| Alzheimer's disease patients | Experimental | To test engineered proteins in human neurons derived from skin biopsy from Alzheimer's disease patients Receives: Other: genetically encoded engineered proteins |
| Neurotypical control patients | Sham comparator | To test engineered proteins in human neurons derived from skin biopsy from neurotypical control patients Receives: Other: genetically encoded engineered proteins |
What is being measured
The primary outcome is the main question the study is designed to answer.
To use genetically encoded engineered proteins to obtain an inducible control of their activity in living human neurons preventing dendritic spines loss
The primary outcome measure will be the change in synaptic density (i.e., number of spines/micrometers) in living human neurons assessed using two-photon laser scanning microscopy.
Measured: 2 years
To leverage genetically encoded engineered proteins to prevent alterations in the morphology of dendritic spines in living human neurons
Here the measure will be the change in dendritic spine morphology (evaluating the subtype of spines, i.e., thin, stubby, mushroom, etc.) in living human neurons assessed using two-photon laser scanning microscopy.
Measured: 2 years
To use genetically encoded engineered proteins to obtain an inducible control of their activity in living human neurons promoting functional synaptic plasticity
The glutamatergic synaptic responses (i.e., AMPA receptor-mediated currents) will be measured in patch-clamp experiments in in living human neurons.
Measured: 2 years
To use genetically encoded engineered proteins to obtain evaluate neuronal excitability in living human neurons
Neuronal excitability (i.e., number of action potentials recorded with depolarizing current injection) will be measured in patch-clamp experiments in in living human neurons.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2024
- Study start19 Dec 2023
- Primary completion30 Dec 2024 (estimated)
- Study completion28 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Fondazione Policlinico Universitario Agostino Gemelli IRCCSThe 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 N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 14 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06372587
- Sponsor's protocol ID
- 5502
- Acronym
- ENERGISE
- Status last verified
- Apr 2024
- First submitted
- 4 Apr 2024
- Last updated
- 18 Apr 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Leveraging Genetically Encoded engiNeered protEins foR Next-Generation alzheImer'S Therapeutics
- ClinicalTrials.gov ID
- NCT06372587
- Acronym / sponsor ID
- ENERGISE / 5502
- Conditions
- Alzheimer Disease
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 14 participants (estimated)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Study start
- 19 Dec 2023 (actual)
- Primary completion
- 30 Dec 2024 (estimated)
- Study completion
- 28 Feb 2027 (estimated)
- First posted
- 18 Apr 2024 (actual)
- 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.
Is this the right time to use next-generation approaches in Alzheimer's disease (AD)? In recent years, several large clinical trials testing treatments for AD have failed, putting the entire field on a reset. AD drug trials have almost exclusively sought to use antibodies targeted toward misfolded amyloid and tau proteins. Of note, although these approaches have failed, they were designed to cover both familial and sporadic forms of AD. On the other hand, the failure in developing new effective drugs is attributed to, but not limited to, the highly heterogeneous nature of AD with multiple underlying hypotheses and multifactorial pathology. The idea underlying this project is based on the assumption that learning and memory disorders can arise when the connections between neurons do not change appropriately in response to experience. Thus, by intervening on the core mechanisms of the cellular correlate of learning and memory, i.e., synaptic plasticity, the investigators expect to preserve some of the essential brain functions in AD. By overcoming the limits of traditional AD therapeutic approaches, the investigators will use genetically encoded engineered proteins (GEEPs), which the investigators developed and tested in vitro and in murine models, to control their activity in living human neurons boosting synaptic plasticity. Indeed, outstanding and relevant progress in understanding synaptic physiology empowers the possibility to prevent or limit brain disease like never before. The investigators designed GEEPs to address some of the leading causes of synaptic plasticity failures documented in AD. Thus, GEEPs will be tested in human induced pluripotent stem cells (hiPSCs)-derived living neurons obtained from reprogrammed peripheral tissues of participants with Alzheimer's diseases. hiPSCs will be obtained from fibroblast-derived from a skin biopsy of participants with AD and controls performed in local anesthesia using a 4 mm punch. The findings will provide the first preclinical study on the effect of genetically engineered proteins to control essential pathways implicated in synaptic plasticity on AD-related cognitive decline.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Alzheimer's disease patients | Experimental | Other: genetically encoded engineered proteinsTo test engineered proteins in human neurons derived from skin biopsy from Alzheimer's disease patients |
| Neurotypical control patients | Sham comparator | Other: genetically encoded engineered proteinsTo test engineered proteins in human neurons derived from skin biopsy from neurotypical control patients |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Manifest clinical criteria for probable AD;
- Age between 18 and 80 years;
- Signed informed consent obtained;
Key exclusion criteria (5 listed)
- Patients suffering from other neurological diseases;
- Patients with coagulation disorders or in treatment with anticoagulant drugs;
- Patients suffering from dermatological diseases and connective tissue diseases;
- Patients suffering from other organic, psychiatric diseases or laboratory abnormalities could preclude participation or invalidate the study results;
- Inability to give informed consent.
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 |
|---|---|---|
| genetically encoded engineered proteinsusing genetically encoded engineered proteins to obtain an inducible control of their activity in living human neurons promoting synaptic plasticity and/or preventing dendritic spines loss | Other | Alzheimer's disease patients, Neurotypical control patients |
Primary outcome
To use genetically encoded engineered proteins to obtain an inducible control of their activity in living human neurons preventing dendritic spines loss
Time frame: 2 years
The primary outcome measure will be the change in synaptic density (i.e., number of spines/micrometers) in living human neurons assessed using two-photon laser scanning microscopy.
To leverage genetically encoded engineered proteins to prevent alterations in the morphology of dendritic spines in living human neurons
Time frame: 2 years
Here the measure will be the change in dendritic spine morphology (evaluating the subtype of spines, i.e., thin, stubby, mushroom, etc.) in living human neurons assessed using two-photon laser scanning microscopy.
To use genetically encoded engineered proteins to obtain an inducible control of their activity in living human neurons promoting functional synaptic plasticity
Time frame: 2 years
The glutamatergic synaptic responses (i.e., AMPA receptor-mediated currents) will be measured in patch-clamp experiments in in living human neurons.
To use genetically encoded engineered proteins to obtain evaluate neuronal excitability in living human neurons
Time frame: 2 years
Neuronal excitability (i.e., number of action potentials recorded with depolarizing current injection) will be measured in patch-clamp experiments in in living human neurons.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2024.
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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.
Fondazione Policlinico Universitario A. Gemelli IRCCS
Roma, Italy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing genetically encoded engineered proteins in people with Alzheimer Disease, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
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 3 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: looking for participants now, as of the sponsor's last update on 18 Apr 2024. 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 Italy. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To use genetically encoded engineered proteins to obtain an inducible control of their activity in living human neurons preventing dendritic spines loss (time frame: 2 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Apr 2024.