Clinical trial NCT03597360: Low Dose Ionizing Radiation Using CT Scans as a Potential Therapy for Alzheimer's Dementia: A Pilot Study
Official title: Low Dose Ionizing Radiation Using CT Scans as a Potential Therapy for Alzheimer's Dementia (LDIR-CT-AD) Trial: A Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Dementia Alzheimers
Lead sponsor: Baycrest
Sponsor class: OTHER
First posted: 2018-07-24
Enrollment: 4
Sex: ALL
Minimum age (years): 70
Maximum age (years): 90
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this project is to determine whether low doses of ionizing radiation (LDIR) from repeat CT scanning improves function, cognition and/or behavior in severe AD.

Detailed description: Alzheimer's dementia (AD) is a disorder of uncertain cause and pathogenesis that primarily affects older adults. It accounts for more than 50 percent of cases of dementia in the elderly and is a leading source of morbidity and mortality in the aging population. The most essential and often earliest symptom is selective memory impairment. While treatments can improve some symptoms, there is no cure or disease-modifying therapy, and the disease inevitably progresses in all patients. The mainstay of management is still symptomatic treatment of behavioral disturbances, environmental manipulations to prevent behavioural disturbances, and counseling with respect to safety issues.

The goal of this project is to determine whether low doses of ionizing radiation (LDIR) from repeat CT scanning improves function, cognition and/or behavior in severe AD. This is based upon the treatments given in 2015 to a patient in hospice in the USA with advanced AD. On July 23, she received two CT scans of her brain. Two weeks later she received a third CT scan, and two weeks after this, a fourth CT scan. She partially improved and was discharged to an Alzheimer care home.

In terms of the mechanism whereby CT scanning might lead to improvement, reactive oxygen species (ROS) are produced abundantly and constantly by aerobic metabolism in all organisms, damaging biomolecules including those in the brain. AD is postulated to be caused by the accumulation of oxidative stress damage in the brain that was not prevented, repaired or removed by the patient's own biological protective mechanisms. These systems, characterized genetically, operate against all toxins regardless of whether they are produced endogenously or by external physical, chemical or biological agents. As people age, their protection systems become progressively weaker. LDIR is postulated to stimulate adaptive protection systems. This may produce beneficial effects including improvement in AD symptoms. With about three-quarters of human tissue being water, most of the initial radiation-induced damage is radiolysis of water, producing ROS and hydrogen peroxide (H2O2). LDIR leads to mild oxidative stress and strong signaling, which up-regulates protection.The degree of stimulation likely depends upon individual genetic factors.

CT scans are approved for clinical diagnostic imaging. Approval will be requested from the Research Ethics Board (REB) at Baycrest Health Sciences and from Health Canada to use CT scanning for the experimental treatment of AD. If this pilot study is successful, i.e., if improvement is observed in the participants, then a proposal will be prepared for more comprehensive clinical studies of this novel treatment.

Eligibility criteria: Inclusion Criteria:

1. Males or females with severe AD dementia (MMSE\<12) between the ages of 70 to 90 years.
2. Meet the criteria of AD (NIA-AA).
3. If on any of the following medications: acetylcholinesterase inhibitors and/or memantine, participants must be on a stable dose for at least 60 days.
4. Clinically stable for at least 3 months.

Exclusion Criteria:

1. Current or past history of malignancy.
2. Previous history of radiotherapy.
3. Neurological disorder other than AD.
4. Currently receiving other experimental treatments.
5. Clinical or imaging evidence of stroke (with more than 1-2 lacunar infarcts on CT scan or MRI).
6. Major depression, bipolar affective disorder or psychosis.

Primary outcomes:
measure: Alzheimer Disease Functional Assessment and Change Scale (ADFACS)
timeFrame: 20 minutes
Secondary outcomes:
measure: Severe Impairment Battery (SIB)
timeFrame: 30 minutes
measure: Cohen-Mansfield Agitation Index (CMAI)
timeFrame: 30 minutes
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Baycrest Health Sciences
state: Ontario
Study officials:
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