Noninvasive brain stimulation for frontotemporal dementia

Non-invasive Brain Stimulation for Gamma-induction and Cognitive Enhancement in FTD (Gamma-Induction in FrontoTemporal Dementia, GIFTeD)

This study is testing if a new type of brain stimulation can safely help people with frontotemporal dementia improve their brain function over six weeks.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 70 (estimated)
• Ages: 40 Years to 85 Years
• Sex: All
• Sponsor: Massachusetts General Hospital (other)
• Drugs / interventions: radiation
• Locations: 2 sites (Boston, Massachusetts and 1 other locations)
• Trial ID: NCT04425148 on ClinicalTrials.gov

What this trial studies

This interventional study investigates the safety, tolerability, and efficacy of 40 Hz transcranial alternating current stimulation (tACS) in patients with frontotemporal dementia (FTD). Participants will undergo a series of assessments including cognitive evaluations, EEG, and FDG-PET imaging before and after a 6-week treatment period of either active or sham tACS. The study aims to explore the potential mechanisms of action of tACS and its effects on brain activity and metabolism. By comparing results from the active and sham groups, the study seeks to inform future larger clinical trials.

Who should consider this trial

Good fit: Ideal candidates are adults aged 40 to 85 diagnosed with probable behavioral variant frontotemporal dementia or semantic variant primary progressive aphasia.

Not a fit: Patients with significant neurodegenerative disorders other than frontotemporal dementia will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new noninvasive treatment option for patients with frontotemporal dementia.

How similar studies have performed: Other studies have shown promise with noninvasive brain stimulation techniques, but this specific approach is relatively novel.

Eligibility criteria

FTD Participants

Inclusion Criteria:

* Diagnosis of probable Frontotemporal dementia (bvFTD or svPPA)
* Mini Mental State Examination (MMSE) \> 18
* FTLD-specific Clinical Dementia Rating (FTLD-CDR) total score of ≤1
* On stable medications related to cognition or behavior for \>30 days such as acetylcholinesterase inhibitors, memantine, anti-depressants, antipsychotic agents, other mood stabilizers, benzodiazepines;
* Age from 40 to 85 years;
* Minimum of completed 8th grade education
* No history of intellectual disability

Exclusion Criteria:

* Current or past history of any significant neurodegenerative disorder of the central nervous system other than FTD e.g. Alzheimer's disease, Lewy body dementia, Parkinson's disease, multiple sclerosis, progressive supranuclear palsy, normal pressure hydrocephalus, Huntington's disease, any condition directly or indirectly caused by Transmissible Spongiform Encephalopathy (TSE), Creutzfeldt-Jakob Disease (CJD), variant Creutzfeldt-Jakob Disease (vCJD), or new variant Creutzfeldt-Jakob Disease (nvCJD);
* Current or past history of stroke (cortical stroke), intracranial brain lesions, 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, psychotic disorders, or any other major psychiatric condition will be evaluated by the study MD.
* Current history of poorly controlled migraines including chronic medication for migraine prevention
* History of seizures with the exception of a single seizure of benign etiology (e.g. febrile seizure) in the judgment of the investigator;
* History of fainting spells of unknown or undetermined etiology that might constitute seizures.
* 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 in the head (except dental), pacemaker, medication pump, nerve stimulator, TENS unit, ventriculo-peritoneal shunt, cochlear implant, unless cleared by the study MD.
* Contraindication for undergoing MRI or receiving TMS or tACS;
* Any clinically significant hematological, endocrine, cardiovascular, renal, hepatic, gastrointestinal or neurological disease. If the condition has been stable for at least the past year and is judged by the investigator not to interfere with the patient's participation in the study, the patient may be included;
* \>50 mSv of radiation exposure for research within the past year (PET imaging exclusion);
* 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).

Healthy Volunteers

Inclusion Criteria:

* Age: 40-85 years
* Normal healthy volunteer
* Right-handed (assessed by means of the Edinburgh Handedness Questionnaire)
* MMSE \>27
* Minimum of completed 8th grade education
* No history of intellectual disability

Exclusion Criteria:

* 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 family history of treatment resistant epilepsy, with the exception of a single seizure of benign etiology (e.g. febrile seizures) in the judgment of the investigator
* History of head injury resulting in prolonged loss of consciousness
* Any metal in the brain, skull or elsewhere unless approved by the responsible MD
* Any medical devices (i.e. Cardiac pacemaker, deep brain stimulator, medication infusion pump, cochlear implant, vagal nerve stimulator) unless otherwise approved by the responsible MD
* Past or current history of major depression, bipolar disorder or psychotic disorders, or any other major psychiatric condition.
* Neurological disorder or intracranial lesion (including an incidental finding on MRI)
* Current history of poorly controlled migraines including chronic medication for migraine prevention
* Any unstable medical condition
* Pregnancy
* Medications will be reviewed by the responsible MD and a decision about inclusion will be made based on the following:

  * The participant's past medical history, drug dose, history of recent medication changes or duration of treatment, and combination with other CNS active drugs.
* Substance abuse or dependence within the past six months
* Subjects who, in the investigator's opinion, might not be suitable for the study
* Diseased or damaged skin over the face or scalp
* A hair style or head dress that prevents electrode contact with the scalp (for example: thick braids, hair weave, afro, wig)

Where this trial is running

Boston, Massachusetts and 1 other locations

• Beth Israel Deaconess Medical Center — Boston, Massachusetts, United States (RECRUITING)
• Fondazione Santa Lucia — Roma, Italy (RECRUITING)

Study contacts

• Principal investigator: Emiliano Santarnecchi, PhD — Massachusetts General Hospital
• Study coordinator: Emiliano Santarnecchi

Conditions: Frontotemporal Dementia, FTD