Clinical trial NCT05256121: HAPPCAP-AD (Human-APPlication Combined Approach for Prevention of Alzheimer's Disease)
Official title: HAPPCAP-AD (Human-APPlication Combined Approach for Prevention of Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Alzheimer Disease
Keywords: Alzheimer Disease; AD offspring; prevention; risk factors
Lead sponsor: Sheba Medical Center
Sponsor class: OTHER_GOV
Collaborators: name: Maccabi Healthcare Services, Israel
First posted: 2022-02-25
Enrollment: 100
Sex: ALL
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Currently, Alzheimer's disease (AD) has no cure putting prevention-strategies in the forefront for impeding the public health and personal consequences of this devastating disease. Seven major potentially modifiable risk factors show consistent association with AD (midlife type 2 diabetes \[T2D\], midlife hypertension, midlife obesity, physical inactivity, depression, smoking, and low educational attainment), with combined population-attributable risk of 30%1. A recent extensive literature review of randomized control trials on single lifestyle interventions for AD yielded negative results. The multidomain preDIVA2,3 (Prevention of Dementia by Intensive Vascular Care) and MAPT4,5 (Multidomain Alzheimer Prevention Trial) studies raised concerns regarding the multidomain approach. The multidomain lifestyle model approach of the FINGER6,7 study (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability) brought some optimism after it presented positive results; several replication trials around the world have been launched8. However, 1) all trials focus on the elderly, 2) the impact of midlife risk factors on dementia risk is stronger than late life, and 3) the neurodegenerative changes in AD begin decades before its clinical manifestations9. A recent study showed that 2 or more cardiovascular risk factors in midlife (but not late life) predicted amyloid aggregation10.

Main goals:

To examine the feasibility and provide pilot data on effectiveness of a novel "real-life" personalized 18-months intervention for prevention of cognitive decline in middle-aged individuals (age 40-65-year-old) at high AD risk due to AD parental family history. We will implement an approach "diary-monitoring" ("Risk factors log" which will filled daily by participants, using the REDCap (Research Electronic Data Capture) software's survey) with study team guidance. We hypothesize that daily risk-factors documentation in personal "Risk factors log" will increase participant's engagement in the intervention and will enable the study team to accumulate health information, in order to improve support and counselling for improvement of risk factors. In addition to examining the feasibility of our approach, we will explore its effectiveness in both improving risk factors values, as well as improving cognitive function by comparing the HAPPCAP-AD intervention group to "control group". Last, our study will lay the foundations for a strong long-term large-scale preventive intervention in the future. We will compare this group to a partially passive control.

Detailed description: To examine the feasibility and provide pilot data on effectiveness of a novel "real-life" personalized 18-months intervention for prevention of cognitive decline in middle-aged individuals (age 40-65-year-old) at high AD risk due to AD parental family history. We will implement an approach "diary-monitoring" ("Risk factors log" which will filled daily by participants, using the REDCap (Research Electronic Data Capture) software's survey) with study team guidance. We hypothesize that daily risk-factors documentation in personal "Risk factors log" will increase participant's engagement in the intervention and will enable the study team to accumulate health information, in order to improve support and counselling for improvement of risk factors. In addition to examining the feasibility of our approach, we will explore its effectiveness in both improving risk factors values, as well as improving cognitive function by comparing the HAPPCAP-AD intervention group to "control group". Last, our study will lay the foundations for a strong long-term large-scale preventive intervention in the future. We will compare this group to a partially passive control.

Eligibility criteria: Inclusion Criteria:

* • Age 40-65 at enrollment to the study

  * Family history of AD-All subjects recruited will have at least 1 parent diagnosed with AD (as specified below)
  * All participant will be MHS (Maccabi Health System) members
  * Participants must have at least two of the seven risk factors for AD (1. Smoking; 2. type 2 diabetes \[T2D\]; 3. Hypertension; 4. obesity/ overweight; 5. low physical inactivity; 6. low educational attainment/ mental activity; 7. depression)
  * No dementia diagnosis
  * Hebrew fluency

Exclusion Criteria:

* Previously diagnosed dementia•
* Any condition expected to limit the adherence to suggested intervention for 18 months
* Any significant neurologic or psychiatric disease

Primary outcomes:
measure: "Risk factors log" response rate
timeFrame: 18 months
Secondary outcomes:
measure: Percent of weekly physical activity time modification in "unbalanced" participants
timeFrame: 18 months
measure: Percent of Body Mass Index (BMI) modification in "unbalanced" participants
timeFrame: 18 months
measure: Percent of number of smoked cigarettes' modification in "unbalanced" participants
timeFrame: 18 months
measure: Percent of systolic blood pressure values modification in "unbalanced" participants
timeFrame: 18 months
measure: Percent of HBA1C% values modification in "unbalanced" participants
timeFrame: 18 months
measure: Percent of depression modification in "unbalanced" participants
timeFrame: 18 months
measure: Global cognitive function change
timeFrame: 18 months
measure: Change of the memory domain
timeFrame: 18 months
measure: Change of the language domain
timeFrame: 18 months
measure: Change of the executive function domain
timeFrame: 18 months
measure: Change of the attention domain
timeFrame: 18 months
Other outcomes:
Locations:
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
Study officials:
affiliation: Sheba Medical Center
name: Ithamar Ganmore, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: