HAPPCAP-AD (Human-APPlication Combined Approach for Prevention of Alzheimer's Disease) (HAPPCAP-AD)

HAPPCAP-AD (Human-APPlication Combined Approach for Prevention of Alzheimer's Disease

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.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Disease
• Intervention / Treatment: Other: AD Risk factors balance

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.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ithamar Ganmore, MD, PhD; Phone Number: +972-3-5309120; Email: itamargan@gmail.com

Study Locations

• Israel
  • Ramat Gan, Israel, 52621
    • Recruiting
    • Sheba Medical Center
    • Contact: Ithamar Ganmore, MD-PhD; Email: ITAMARGAN@GMAIL.COM

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: control; At 6 months and 12months the study team will communicate with the participants by phone to inquire about risk factors data, propose alternative activities, and provide positive reinforcement and feedback
Experimental: intervention; At baseline, participants in the intervention group will be asked to fill a daily "risk-factor diaries" ("Risk factors log" using the REDCap (Research Electronic Data Capture) software's survey). In the "Risk factors log", participants will need to answer shortly questions about their specific unbalanced risk factor. In addition, during the 18-months intervention period, the study team will communicate with the participants' every 3-4 weeks by phone. Before each phone call, participants' "Risk factors log" data since previous phone call will be analyzed. The team will propose alternative activities, and provide positive reinforcement and feedback.	Other: AD Risk factors balance; At baseline, participants in the intervention group will be asked to fill a daily "risk-factor diaries" ("Risk factors log" using the REDCap (Research Electronic Data Capture) software's survey). In the "Risk factors log", participants will need to answer shortly questions about their specific unbalanced risk factor. In addition, during the 18-months intervention period, the study team will communicate with the participants by phone every 3-4 weeks to inquire about risk factors data. Before each phone call, participants' "Risk factors log" data since previous phone call will be analyzed. The team will propose alternative activities, and provide positive reinforcement and feedback.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
"Risk factors log" response rate	"Risk factors log" response rate will be measured as an adherence to the intervention surrogate (response rate will be calculated as the number of submitted daily "Risk factors logs" divided by number of days in the study)	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of weekly physical activity time modification in "unbalanced" participants	For participants with less than 150 minutes of weekly physical activity at baseline , percentage of relative change between weekly physical activity time (in minutes) values at baseline and 18 months (will be calculated as {([time at 18 months/ time at base line]-1)*100}.	18 months
Percent of Body Mass Index (BMI) modification in "unbalanced" participants	For participants with BMI greater than 25 kg/m2 at baseline, percentage of relative change between BMI (BMI values at baseline and 18 months (will be calculated as {([BMI at 18 months/ BMI at base line]-1)*100}.	18 months
Percent of number of smoked cigarettes' modification in "unbalanced" participants	For participants who smoke at baseline, percentage of relative change between number of smoked cigarettes (number of smoked cigarettes at baseline and 18 months (will be calculated as {([number of smoked cigarettes at 18 months/ number of smoked cigarettes at base line]-1)*100}.	18 months
Percent of systolic blood pressure values modification in "unbalanced" participants	For participants with hypertension at baseline (worse than 125/85 mm Hg), percentage of relative change between systolic blood pressure (in mm Hg at baseline and 18 months (will be calculated as {([systolic blood pressure at 18 months/ systolic blood pressure at base line]-1)*100}.	18 months
Percent of HBA1C% values modification in "unbalanced" participants	For participants with unbalanced diabetes at baseline, percentage of relative change between HBA1C% (at baseline and 18 months (will be calculated as {([HBA1C% at 18 months/ HBA1C% at base line]-1)*100}.	18 months
Percent of depression modification in "unbalanced" participants	For participants with unbalanced depression at baseline, percentage of relative change between number of participants with depression according to their CES-D (Center for Epidemiologic Studies Depression Scale) questionnaire total score (at baseline and 18 months (will be calculated as {([CES-D total score at 18 months/ CES-D total score at base line]-1)*100}.	18 months
Global cognitive function change	The influence of study intervention on global cognitive function will be assessed by calculating the changes in global cognitive function using a Z score between baseline and after 18 month (this is an exploratory aim since this is a pilot study). (Global cognition z score was obtained by averaging the domains [memory, language, executive function, attention] z scores) Higher Z score represent better global cognitive function	18 months
Change of the memory domain	The influence of study intervention on memory domain will be assessed by calculating the changes in memory function using a Z score between baseline and after 18 month (this is an exploratory aim since this is a pilot study). Higher Z score represent better memory function	18 months
Change of the language domain	The influence of study intervention on language domain will be assessed by calculating the changes in language function using a Z score between baseline and after 18 month (this is an exploratory aim since this is a pilot study). Higher Z score represent better language function	18 months
Change of the executive function domain	The influence of study intervention on executive function domain will be assessed by calculating the changes in executive function domain using a Z score between baseline and after 18 month (this is an exploratory aim since this is a pilot study). Higher Z score represent better executive function domain function	18 months
Change of the attention domain	The influence of study intervention on attention domain will be assessed by calculating the changes in attention domain using a Z score between baseline and after 18 month (this is an exploratory aim since this is a pilot study). Higher Z score represent better attention function	18 months

Collaborators and Investigators

• Sponsor: Sheba Medical Center
• Collaborators: Maccabi Healthcare Services, Israel
• Investigators: Principal Investigator: Ithamar Ganmore, MD, PhD, Sheba Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2019
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: May 6, 2019
• First Submitted That Met QC Criteria: February 24, 2022
• First Posted (Actual): February 25, 2022

Study Record Updates

• Last Update Posted (Actual): May 24, 2022
• Last Update Submitted That Met QC Criteria: May 22, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Alzheimer Disease; AD offspring; prevention; risk factors
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: SHEBA-18-5744-IG-CTIL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Participants will sign if they agree that their data will be shared anonymously with other AD/ cognition/ other studies
• IPD Sharing Time Frame: Undecided yet
• IPD Sharing Access Criteria: Undecided yet
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No