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Behavioural Intervention

TMS for Alzheimer's Disease (PROMIS-AD Trial)

Phase 1 & 2

Recruiting

Led By Michael Leuchter, MD

Research Sponsored by University of California, Los Angeles

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age 60-100 at the start of the study

Established diagnosis of Alzheimer's Clinical Syndrome (which is also met through a diagnosis of Alzheimer's Dementia)

Must not have

Participant and/or their surrogate are unwilling or unable to provide informed consent

Diagnosis of a dementia or cognitive disorder due to a cause other than Alzheimer's Disease

Timeline

Screening 3 weeks

Treatment Varies

Follow Up enrollment to end of 5 weeks of treatment

Summary

This trial aims to see if using deep repetitive transcranial magnetic stimulation (rTMS) on a specific part of the brain can help improve memory in individuals with Probable Alzheimer's Dementia.

Who is the study for?

This trial is for individuals with mild-to-moderate probable Alzheimer's Dementia. Participants will undergo memory testing, brain scans, and bloodwork. They must be able to visit the clinic for multiple rTMS sessions.

What is being tested?

The study tests if deep repetitive transcranial magnetic stimulation (rTMS) targeting the precuneus can improve memory in Alzheimer's patients. It compares active stimulation with placebo while monitoring brain changes through various assessments.

What are the potential side effects?

While not explicitly listed, common side effects of rTMS may include headache, scalp discomfort at the site of stimulation, tingling or spasms of facial muscles, lightheadedness.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 60 and 100 years old.

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I have been diagnosed with Alzheimer's disease.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am unable or unwilling to give consent for treatment.

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My dementia is not caused by Alzheimer's Disease.

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I have uncontrolled high blood pressure or heart/stroke issues.

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I have had TMS treatment before.

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I have not been treated with specific monoclonal antibodies for Alzheimer's.

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I or a close family member have had seizures.

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I cannot have MRI or TMS due to metal in my body, recent surgery, certain implants, or claustrophobia.

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I have had a stroke, traumatic brain injury, or a major neurological disorder.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from enrollment until the end of treatment at 5 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from enrollment until the end of treatment at 5 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and from enrollment until the end of treatment at 5 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Completion Rate

Secondary study objectives

Adverse Events

Clinical Dementia Rating Scale (CDR)

EEG

+4 more

Other study objectives

ADL/IADL

Geriatric Depression Scale (GDS)

Mini-Mental State Examination (MMSE)

+5 more

Side effects data

From 2018 Phase 1 & 2 trial • 92 Patients • NCT00520130

64%

ALT, SGPT (serum glutamic pyruvic transaminase)

61%

Leukocytes (total WBC)

61%

Lymphopenia

59%

AST, SGOT(serum glutamic oxaloacetic transaminase)

59%

Hemoglobin

59%

Neutrophils/granulocytes (ANC/AGC)

57%

Platelets

45%

Infection with normal ANC or Grade 1 or 2 neutrophils::Blood

45%

Diarrhea

45%

Phosphate, serum-low (hypophosphatemia)

43%

Rash/desquamation

36%

Nausea

30%

Magnesium, serum-high (hypermagnesemia)

27%

Bilirubin (hyperbilirubinemia)

23%

Mucositis/stomatitis (clinical exam)::Oral cavity

23%

Infection with normal ANC or Grade 1 or 2 neutrophils::Lung (pneumonia)

23%

Renal failure

23%

Potassium, serum-low (hypokalemia)

20%

Creatinine

20%

Albumin, serum-low (hypoalbuminemia)

20%

Infection::Blood

20%

Infection with normal ANC or Grade 1 or 2 neutrophils::Upper airway NOS

18%

Dry eye syndrome

18%

Mucositis/stomatitis (functional/symptomatic)::Oral cavity

16%

Hypoxia

16%

Alkaline phosphatase

14%

Febrile neutropenia

14%

Infection ::Bladder (urinary)

14%

Infection ::Lung (pneumonia)

14%

Infection with unknown ANC::Upper airway NOS

14%

Sodium, serum-low (hyponatremia)

14%

Thrombosis/thrombus/embolism

11%

Colitis, infectious (e.g., Clostridium difficile)

11%

PTT (Partial Thromboplastin Time)

Death not associated with CTCAE term::Death NOS

Dyspnea (shortness of breath)

Infection with normal ANC or Grade 1 or 2 neutrophils::Catheter-related

Infection with normal ANC or Grade 1 or 2 neutrophils::Sinus

Dry mouth/salivary gland (xerostomia)

Hyperpigmentation

Induration/fibrosis (skin and subcutaneous tissue)

Infection with normal ANC or Grade 1 or 2 neutrophils::Urinary tract NOS

Infection with unknown ANC::Blood

Neuropathy: sensory

Renal/Genitourinary - Other (insufficiency)

Uric acid, serum-high (hyperuricemia)

Magnesium, serum-low (hypomagnesemia)

Death not associated with CTCAE term::Disease progression NOS

Infection ::Blood

Hypotension

Infection with normal ANC or Grade 1 or 2 neutrophils::Brain (encephalitis, infectious)

Supraventricular and nodal arrhythmia::Atrial fibrillation

Carbon monoxide diffusion capacity (DL(co))

Dysphagia (difficulty swallowing)

Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)

GGT (gamma-Glutamyl transpeptidase)

Gastritis (including bile reflux gastritis)

Heartburn/dyspepsia

Hemorrhage, GU::Bladder

Hypertension

Infection with normal ANC or Grade 1 or 2 neutrophils::Bladder (urinary)

Pancreatic endocrine: glucose intolerance

Potassium, serum-high (hyperkalemia)

Rash: acne/acneiform

Renal/Genitourinary - Other (acute renal injury)

Pleural effusion (non-malignant)

Pain::Muscle

Dermatology/Skin - Other (GVHD; cGVHD)

Metabolic/Laboratory - Other (pancytopenia; steroid induced hyperglycemia)

Allergic reaction/hypersensitivity (including drug fever)

Infection::Sinus

Infection ::Urinary tract NOS

Infection with normal ANC or Grade 1 or 2 neutrophils::Bronchus

Infection with normal ANC or Grade 1 or 2 neutrophils::Pharynx

Infection with normal ANC or Grade 1 or 2 neutrophils::Skin (cellulitis)

Infection with unknown ANC::Lung (pneumonia)

Left ventricular systolic dysfunction

Pericardial effusion (non-malignant)

Pneumonitis/pulmonary infiltrates

Thrombosis/embolism (vascular access-related)

Thrombotic microangiopathy

Anorexia

FEV(1)

Fatigue (asthenia, lethargy, malaise)

Gastrointestinal - Other (GVHD)

Infection::Bronchus

Infection ::Colon

Infection Sinus

Infection::Urinary tract NOS

Infection - Other (Varicella zoster; noravirus)

Infection with normal ANC or Grade 1 or 2 neutrophils::Colon

Infection with normal ANC or Grade 1 or 2 neutrophils::Nose

Neuropathy: motor

Pain::Anus

Pain::Head/headache

Ulceration

Vaginal dryness

Vomiting

Mood alteration::Anxiety

Iron overload

Cough

Insomnia

Edema: viscera

Pain::Throat/pharynx/larynx

Joint-function

Infection::Catheter-related

Rash: hand-foot skin reaction

Memory impairment

Mood alteration::Depression

Infection::Rectum

Cystitis

Arthritis (non-septic)

Cardiac ischemia/infarction

Cardiopulmonary arrest, cause unknown (non-fatal)

Cholecystitis

Death not associated with CTCAE term::Multi-organ failure

Dermatology/Skin - Other (Deep sclerosis per MRI, GVHD possible)

Confusion

Edema: limb

Hemorrhage, pulmonary/upper respiratory::Lung

Ileus, GI (functional obstruction of bowel, i.e., neuroconstipation)

Infection::Meninges (meningitis)

Infection ::Trachea

Infection with normal ANC or Grade 1 or 2 neutrophils::Esophagus

Infection with normal ANC or Grade 1 or 2 neutrophils::Heart (endocarditis)

Infection with normal ANC or Grade 1 or 2 neutrophils::Wound

Infection with unknown ANC::Catheter-related

Infection with normal ANC or Grade 1 or 2 neutrophils::Liver

Infection with normal ANC or Grade 1 or 2 neutrophils::Meninges (meningitis)

Infection with normal ANC or Grade 1 or 2 neutrophils::Paranasal

Infection with unknown ANC::Colon

Left ventricular diastolic dysfunction

Liver dysfunction/failure (clinical)

Pain::Abdomen NOS

Perforation, GI::Small bowel NOS

Pulmonary/Upper Respiratory - Other (Specify, respiratory failure)

Secondary Malignancy - possibly related to cancer treatment (metastat. test cancer in lung)

Stricture/stenosis (including anastomotic), GI::Esophagus

Ulcer, GI::Duodenum

Adult Respiratory Distress Syndrome (ARDS)

Alkalosis (metabolic or respiratory)

Amylase

Bicarbonate, serum-low

Bronchospasm, wheezing

CPK (creatine phosphokinase)

Cardiac General - Other (cardimyopathy)

Cardiac General - Other (heart failure, fluid overload)

Colitis

Dry skin

Encephalopathy

Esophagitis

Fibrinogen

Fistula, GI::Anus

Glucose, serum-high (hyperglycemia)

Hemolysis (e.g., immune hemolytic anemia, drug-related hemolysis)

Hemorrhage, GI::Abdomen NOS

Hemorrhage, GI::Anus

Hemorrhage, GI::Lower GI NOS

Infection ::Catheter-related

Infection ::Eye NOS

Infection::Skin (cellulites)

Infection::Soft tissue NOS

Infection ::Upper aerodigestive NOS

Infection:: Upper airway NOS

Infection with normal ANC or Grade 1 or 2 neutrophils::Stomach

Infection with normal ANC or Grade 1 or 2 neutrophils::Upper aerodigestive NOS

Infection with unknown ANC::Sinus

Infection with unknown ANC::Urinary tract NOS

Infection with unknown ANC::Wound

Lipase

Myocarditis

Ophthalmoplegia/diplopia (double vision)

Osteonecrosis (avascular necrosis)

Pain::Back

Pain::Urethra

Prolonged QTc interval

Psychosis (hallucinations/delusions)

Pulmonary/Upper Respiratory - Other (infiltrates; fungal pneumonia)

Renal/Genitourinary - Other (dysuria)

Renal/Genitourinary - Other (dysuria; hematuria; stent replacement)

Renal/Genitourinary - Other (fluid overload refractory to normal doses of Lasix)

Renal/Genitourinary - Other (hematuria)

Secondary Malignancy - possibly related to cancer treatment (mucoepidermoid carcinoma)

Secondary Malignancy - possibly related to cancer treatment (squamous cell carcinoma lip)

Skin breakdown/decubitus ulcer

Sodium, serum-high (hypernatremia)

Supraventricular and nodal arrhythmia::Sinus tachycardia

Triglyceride, serum-high (hypertriglyceridemia)

Urinary frequency/urgency

Urinary retention (including neurogenic bladder)

Vaginal mucositis

Weight loss

Infection - Other

Adrenal insufficiency

Phlebitis (including superficial thrombosis)

100%

80%

60%

40%

20%

Study treatment Arm

A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm

B - Cyclosporine (AC) Arm

Trial Design

3Treatment groups

Experimental Treatment

Placebo Group

Group I: Randomized Active deep precuneus rTMSExperimental Treatment1 Intervention

The second stage of the study will consist of both active and sham treatment groups. Treatment will consist of 16 sessions of deep rTMS spread over 5 weeks. The induction phase of treatment will be 4 sessions per day for 3 consecutive days (with 60 minutes between sessions), followed by 1 session per week for 4 weeks. Individual sessions will consist of 1600 pulses of 20Hz rTMS delivered in 40 pulse trains to the precuneus (using MRI structural neuronavigation) at 100% of depth-corrected motor-threshold with a 28 second intertrain interval (roughly 20 minutes per session). The active group will receive this protocol using an active treatment coil delivering real rTMS.

Group II: Open-Label Active deep rTMSExperimental Treatment1 Intervention

The first stage of the study will consist of protocol refinement. In this first stage of 5-10 participants, all participants will receive open-label active treatment. Treatment will consist of 16 sessions of deep rTMS spread over 5 weeks. The induction phase of treatment will be 4 sessions per day for 3 consecutive days (with 60 minutes between sessions), followed by 1 session per week for 4 weeks. Individual sessions will consist of 1600 pulses of 20Hz rTMS delivered in 40 pulse trains to the precuneus (using MRI structural neuronavigation) at 100% of depth-corrected motor-threshold with a 28 second intertrain interval (roughly 20 minutes per session).

Group III: Randomized Sham deep precuneus rTMSPlacebo Group2 Interventions

The second stage of the study will consist of both active and sham treatment groups. Treatment will consist of 16 sessions of deep rTMS spread over 5 weeks. The induction phase of treatment will be 4 sessions per day for 3 consecutive days (with 60 minutes between sessions), followed by 1 session per week for 4 weeks. Individual sessions will consist of 1600 pulses of 20Hz rTMS delivered in 40 pulse trains to the precuneus (using MRI structural neuronavigation) at 100% of depth-corrected motor-threshold with a 28 second intertrain interval (roughly 20 minutes per session). The placebo group will receive this protocol using a sham TMS coil delivering inactive rTMS. Participants in the sham/placebo group will be offered a full open-label extension treatment course of active rTMS on completion of the randomized phase.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

TMS

2021

Completed Phase 2

~2170

0 / 10Eligibility criteria met