Gamma Induction for Amyloid Clearance in Alzheimer's Disease

Plain English Summary

Gamma Induction for Alzheimer's Disease is a Phase 2 clinical trial sponsored by Massachusetts General Hospital studying Alzheimer Disease, Mild Cognitive Impairment. This trial tests a non-invasive brain stimulation technique called tACS to see if it can reduce harmful protein buildup (amyloid and tau) in the brains of people with Alzheimer's. It is for individuals diagnosed with early to moderate Alzheimer's disease who have confirmed amyloid buildup in their brain. Participants will receive multiple daily sessions of brain stimulation or a placebo over several weeks, with regular assessments of safety and cognitive function. Current treatments for Alzheimer's primarily manage symptoms; this trial aims to explore a treatment that could potentially slow or reverse disease progression. The trial aims to enroll 17 participants.

Official Summary

Alzheimer's Disease (AD) is characterized by amyloid-β (Aβ) plaque buildup and phosphorylated tau (p-tau) in the brain, as well as widespread neurodegeneration. Amyloid-β and tau are proteins that build up in the brain that may contribute to memory problems. The evidence suggests that both amyloid and tau play a critical role in AD and interventions that reliably and safely decrease the intracerebral burden of amyloid or tau could potentially be of marked clinical importance. Currently, therapeutic options are very limited and while there are pharmacologic interventions that transiently improve cognitive function, there are no treatments that alter disease progression. The purpose of this study is to see if multiple daily sessions of non-invasive brain stimulation can affect brain activity to decrease the amount of amyloid and tau in people with AD as compared to Sham (placebo) stimulation. The type of brain stimulation that will be used is called transcranial alternating current stimulation (tACS). This study will investigate different doses of tACS (2-4 weeks) and assess safety. The hope is that tACS will decrease the amount of amyloid and tau and improve memory and thinking in people with AD.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you have early to moderate Alzheimer's, a certain score on cognitive tests (MMSE >= 18, CDR >= 0.5), and confirmed amyloid buildup in your brain via PET scan. You must be at least 45 years old and on a stable dose of Alzheimer's medications for at least 6 weeks. You cannot join if you have a history of seizures, major psychiatric disorders, recent significant head trauma, or certain neurological conditions. Certain medical implants, recent radiation exposure for research, or conditions that could cause a medical emergency during stimulation are also exclusion criteria. This trial is studying Alzheimer Disease, Mild Cognitive Impairment, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcomes measure the amount of amyloid and tau proteins in the brain and changes in cognitive function, indicating whether the stimulation therapy is successfully clearing these proteins a The specific primary outcome measures are: PET amyloid burden (up to 16 weeks); PET tau deposition (up to 16 weeks); Incidence of Treatment-Emergent Adverse Events (up to 16 weeks); Change in Gamma activity (up to 16 weeks); Alzheimer's Disease Assessment Scale -Cog Score (up to 16 weeks). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a critical need for treatments that can modify the underlying disease process of Alzheimer's by targeting the buildup of amyloid and tau proteins, which current therapies do not e Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Alzheimer Disease, Mild Cognitive Impairment, where improved treatment options are needed.

Investor Insight

This Phase 2 trial explores a novel, non-invasive therapeutic approach for Alzheimer's, a condition with a large and growing market, suggesting potential for significant future investment if successfu Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific tACS device used, the duration of treatment, and how your progress will be monitored. Participation involves regular visits for brain stimulation sessions, cognitive assessments, and safety monitoring, including PET scans. Be prepared for potential side effects and discuss any concerns about your daily routine or ability to attend all scheduled sessions. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: QUADRUPLE
• Enrollment: 17 participants

Interventions

• DEVICE: Transcranial Alternating Current Stimulation (tACS) — tACS is a non-invasive way of stimulating the brain externally using weak electric currents. Electrodes are placed into a cap that you wear on your head. A weak electrical current travels back and forth through the electrodes to your head. tACS will be applied at a frequency of 40Hz and targeting the area of maximal tracer uptake on amyloid PET imaging using an individualized multielectrode design to maximize the induced electrical current to the target region.
• OTHER: Sham Transcranial Alternating Current Stimulation — Placebo Control, simulation of transcranial alternating current stimulation without receiving any stimulation

Primary Outcomes

• PET amyloid burden (up to 16 weeks)
• PET tau deposition (up to 16 weeks)
• Incidence of Treatment-Emergent Adverse Events (up to 16 weeks)
• Change in Gamma activity (up to 16 weeks)
• Alzheimer's Disease Assessment Scale -Cog Score (up to 16 weeks)

Secondary Outcomes

• Follow-up Amyloid PET burden (up to 16 weeks)
• Follow-up Cognitive Evaluation (up to 16 weeks)

Full Eligibility Criteria

Inclusion Criteria:

* Clinical Diagnosis of early to moderate AD\*

  * Mini Mental State Examination (MMSE) ≥ 18
  * Clinical Dementia Rating (CDR) ≥ 0.5
  * Demonstration or history of memory impairments.

    * Confirmation of diagnosis will be made by the study MD based on a holistic consideration of the participant's cognitive evaluation and history.
* Amyloid positive PET imaging
* At least 45 years old
* On a stable dose of medications for memory loss including cholinesterase inhibitors (e.g. donepezil, rivastigmine or memantine) as defined as 6 consecutive weeks of treatment at an unchanging dose
* Minimum of completed 8th grade education
* No history of intellectual disability

Exclusion Criteria:

* Current history of poorly controlled migraines including chronic medication for migraine prevention
* Current or past history of any neurological disorder other than dementia, such as epilepsy, stroke (cortical stroke), progressive neurologic disease (e.g. multiple sclerosis) or intracranial brain lesions; and history of previous neurosurgery or head trauma that resulted in residual neurologic impairment.

  * Non-cortical disease such as confluence white matter changes (including lacunar infarcts \< 1cm) and asymptomatic, subacute, cerebellar infarcts may be included upon review of a medically responsible neurologist.
* Past or current history of major depression, bipolar disorder or psychotic disorders, or any other major psychiatric condition.
* Contraindication for undergoing MRI or receiving TMS or tACS,
* \>50 mSv of radiation exposure for research within the past year (PET imaging exclusion)
* History of fainting spells of unknown or undetermined etiology that might constitute seizures.
* History of seizures, diagnosis of epilepsy, history of abnormal (epileptiform) EEG or immediate (1st degree relative) family history of epilepsy; with the exception of a single seizure of benign etiology (e.g. febrile seizure) in the judgment of the investigator.
* Chronic (particularly) uncontrolled medical conditions that may cause a medical emergency in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma, etc.).
* Metal implants (excluding dental fillings) or devices such as pacemaker, medication pump, nerve stimulator, TENS unit, ventriculo-peritoneal shunt, cochlear implant, unless cleared by the study MD.
* Substance abuse or dependence within the past six months.
* Medications will be reviewed by the responsible MD and a decision about inclusion will be made based on the following: The patient's past medical history, drug dose, history of recent medication changes or duration of treatment, and combination of CNS active drugs.
* All female participants that are pre-menopausal will be required to have a pregnancy test; any participant who is pregnant or breastfeeding will not be enrolled in the study.
* Subjects who, in the investigator's opinion, might not be suitable for the study
* A hair style or head dress that prevents electrode contact with the scalp or would interfere with the stimulation (for example: thick braids, hair weave, afro, wig)

Trial Locations

• Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States

Frequently Asked Questions

Related Conditions

• Alzheimer Disease
• Mild Cognitive Impairment
• Dementia
• Neurodegenerative Diseases
• Amyloidosis
• Tauopathy
• Cognitive Impairment
• Geriatric Psychiatry
• Neurology
• Brain Stimulation

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