CLearing Alzheimer's Disease Molecular Pathology Without Medications (CLAMP)

According to the most popular pathophysiological models of Alzheimer's disease, the amyloid hypothesis, amyloid deposition is the causative event triggering a chain of other downstream events which finally lead to Alzheimer's disease and dementia. In mouse models of Alzheimer's disease, 40 Hz multi-sensory (auditory and visual) stimulation was able to reduce the number and size of amyloid plaques throughout cortex and improve cognitive performance.

The primary objective of this study is to assess whether an intervention consisting of 40 Hz multi-sensory (auditory and visual) stimulation is able to reduce the amyloid load in non-demented amyloid-positive individuals.

As secondary objectives, the investigators will assess whether such intervention is able to:

• improve the brain electrical activity,
• improve or slow down the worsening of Alzheimer's blood-based biomarkers,
• improve or slow down the worsening of cognition.

Study Overview

• Status: Not yet recruiting
• Conditions: Amyloidosis; Alzheimer Disease; Amyloid Plaque
• Intervention / Treatment: Other: 40 Hz multi-sensory (auditory + visual) stimulation and cognitive training; Other: Cognitive training

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Informed Consent as documented by signature (Appendix Informed Consent Form),
• age 40-80,
• ≥5 years of education,
• previous evidence of brain amyloidosis (assessed by PET, CSF, or blood-based biomarkers).

Exclusion Criteria:

• history of epilepsy;
• clinically relevant visual or auditory diseases/deficits;
• clinical diagnosis of dementia;
• contraindication to amyloid-PET;
• inability to undergo the procedures of the study, e.g. severe behavioral disturbances;

• severe diseases:

  1. Malignant neoplasm within 5 years,
  2. Life threatening diseases,
  3. Severe systemic diseases (e.g. kidney insufficiency, cardiac insufficiency, decompensated diabetes, decompensated metabolic diseases, decompensated hypothyroidism, uncontrolled autoimmune diseases);
• the participation to a clinical trial involving potential Alzheimer's disease modifying therapies;
• documented pregnancy or intention to become pregnant during the course of the study or breast feeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 40 Hz multi-sensory (auditory + visual) stimulation and cognitive training; 40 Hz multi-sensory (auditory + visual) stimulation and cognitive training (1 hour/day, per 5 days/week, for a total of 8 weeks).	Other: 40 Hz multi-sensory (auditory + visual) stimulation and cognitive training; 40 Hz multi-sensory (auditory + visual) stimulation and cognitive training (1 hour/day, per 5 days/week, for a total of 8 weeks)
Active Comparator: Cognitive training only; Cognitive training only (1 hour per day, per 5 days/week, for a total of 8 weeks).	Other: Cognitive training; Cognitive training (1 hour/day, per 5 days/week, for a total of 8 weeks)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in amyloid load	Changes in amyloid load assessed by longitudinal amyloid-PET	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in brain electrical activity	Changes in brain electrical activity (e.g. gamma power spectral density) assessed by longitudinal EEG	8 weeks
Changes in Alzheimer's blood-based biomarkers	Changes in Alzheimer's blood-based biomarkers (e.g. plasma Aβ42/Aβ40 ratio, Aβ42, Aβ40, p-tau, and neurofilament light) assessed by longitudinal blood sample collection	8 weeks
Changes in cognition	Changes in cognition (using the Preclinical Alzheimer Cognitive Composite (PACC) score) assessed by longitudinal neuropsychological assessment	8 weeks

Collaborators and Investigators

• Sponsor: University Hospital, Geneva

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2021
• Primary Completion (Anticipated): June 30, 2022
• Study Completion (Anticipated): July 31, 2022

Study Registration Dates

• First Submitted: May 25, 2021
• First Submitted That Met QC Criteria: May 28, 2021
• First Posted (Actual): June 4, 2021

Study Record Updates

• Last Update Posted (Actual): June 4, 2021
• Last Update Submitted That Met QC Criteria: May 28, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Pathological Conditions, Anatomical; Proteostasis Deficiencies; Dementia; Tauopathies; Amyloidosis; Alzheimer Disease; Plaque, Amyloid
• Other Study ID Numbers: 2021-00989

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No