Clinical trial NCT03688126: U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk
Official title: U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Alzheimer Disease
Keywords: cognitive decline
dementia
cognitive function
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: Alzheimer's Association
First posted: 2018-09-28
Enrollment: 2000
Sex: ALL
Minimum age (years): 60
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: The purpose of this research study is to see if lifestyle changes can protect memory and thinking (cognition) as we age. A recent study in Finland found that a combination of physical and cognitive exercise, diet, and social activity protected cognitive function in healthy older adults who were at increased risk of significant memory loss. So far no medications can rival this positive outcome. The point of POINTER is to test if lifestyle change can also protect against memory loss in Americans.

Detailed description: Lifestyle interventions focused on combining healthy diet, physical activity, and social and intellectual challenges may represent a promising therapeutic strategy to protect brain health. The recent results of the population-based 2-year clinical trial, Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), indicated that a multidomain intervention of physical activity, nutritional guidance, cognitive training, social activities, and management of heart health risk factors protected cognitive function in healthy older adults at increased risk of cognitive decline. As yet, there are no pharmacological treatment options that can rival this effect. Thus, there is an urgent need to expand this work to test the generalizability, adaptability and sustainability of its findings in diverse and global populations. This pivotal U.S. Study to Protect Brain Health through Lifestyle Intervention to Reduce Risk (U.S. POINTER) will test whether a similar 2-year intensive lifestyle intervention, adapted to American culture and delivered within the community, can protect cognitive function in older adults in the U.S. who are at increased risk for cognitive decline and dementia. If successful, the results of this study will have large-scale implications for public policy regarding standard of clinical care and prescriptive practices for a fast-growing and vulnerable population of older adults.

Eligibility criteria: Inclusion Criteria:

* Sedentary (not a regular exerciser, determined using the POINTER--modified Telephone Assessment of Physical Activity \[TAPA\]
* Low MIND Diet score (determined using the MIND Diet Screener)
* No cognitive impairment as per Telephone Interview for Cognitive Status (mTICS) score \>32 (includes adjustments for demographics such as age, education and race), the Clinical Dementia Rating Scale (CDR \<0.5), and the CDR-Sum of Boxes (CDR-SB \<1)
* Risk Score for cognitive decline \>2, using the following scoring algorithm:1 point: Suboptimum cardiovascular health (treated or untreated): systolic Blood Pressure \>125 mmHg \~OR\~ low-density lipoprotein (LDL) cholesterol \>115 mg/dL\~OR\~ glycated hemoglobin (HbA1c) \>6.0%1 point: First degree family history (mother, father, sister, brother) of memory impairment- 1 point: Race and ethnicity: African American/Black, Native American, Middle Eastern/North African, or Hispanic/Latinx

  1 point: Older age: 70-79 years 1 point: Sex: male
* Lives in a region where the POINTER interventions will be delivered
* Does not plan to travel outside of the home geographic area for an extended period of time during study participation
* Capacity to complete physical exercise
* Willing to complete all study-related activities for at least 24 months
* Willing to be randomized to either lifestyle intervention group

Exclusion Criteria

* Age \<60 or ≥80 years
* Any significant neurologic disease, including any form of dementia, mild cognitive impairment, Parkinson's disease, Huntington's disease, normal pressure hydrocephalus, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma with persistent neurologic sequelae or known structural brain abnormalities
* History of major depression within the last 6 months
* History of bipolar disorder or schizophrenia as per Diagnostic and Statistical Manual (DSM) V criteria
* History of alcohol or substance abuse or dependence within the past 2 years, as per DSM V criteria
* Current or past use of medications for memory impairment or AD (e.g., cholinesterase inhibitors, memantine)
* Current daily use of systemic corticosteroids
* Current use of 3 or more doses of narcotics/week. Use of intermittent narcotics should be stopped 48 hours prior to clinic visits/cognitive testing. Tramadol is allowed as long as the dose remains stable for 3 months.
* Use of psychoactive medications, including benzodiazepines, tricyclic antidepressants, antipsychotics, mood-stabilizers, psychostimulants, anti- parkinsonian medications, anticonvulsant medications or medications with significant central anticholinergic activity are allowed as long as the medication is NOT used to treat an exclusionary medical condition.
* Significant cardiovascular disease (including New York Heart Association (NYHA) Class III or IV congestive heart failure, clinically significant aortic stenosis, history of cardiac arrest, or uncontrolled angina)
* Serious conduction disorder (e.g., 3rd degree heart block), uncontrolled arrhythmia, or new Q waves or ST-segment depressions (\>3 mm) on ECG (treated atrial fibrillation for more than 1 year or occasional premature ventricular contractions on ECG are not exclusions)
* Myocardial infarction, major heart surgery (i.e., valve replacement, bypass surgery, stent placement, angioplasty), deep vein thrombosis, or pulmonary embolus in the past 6 months
* Large vessel stroke in the past 2 years
* History of transient ischemic attack (TIA) or small vessel stroke in the last 6 months; TIA occurring more than 6 months ago with residual effects
* Current use of insulin to treat type 2 diabetes
* Lung disease requiring either regular use of corticosteroids or the use of supplemental oxygen; intermittent use of corticosteroids or supplemental oxygen to treat chronic obstructive pulmonary disease exacerbation is allowed; use of inhaled steroids for asthma is allowed
* End stage renal disease (e.g., requiring dialysis or as per clinician discretion)
* Clinically significant abnormalities in laboratory blood tests as per judgment of the site Study Clinician
* History within the last 2 years of treatment for primary or recurrent malignant disease, excluding non-melanoma skin cancers, resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with normal prostate-specific antigen post treatment; long-term endocrine therapy for breast cancer is allowed (e.g., tamoxifen, anastrozole)
* History of hip fracture, joint replacement, or spinal surgery in the last 6 months
* Currently receiving physical therapy or cardiopulmonary rehabilitation
* History of a malabsorptive bariatric procedure (gastric bypass, biliopancreatic diversion); other bariatric procedures involving restriction (i.e., sleeve, band) are not exclusionary
* Resides in an assisted living facility or nursing home
* Receives hospice care
* Site PI/Study Clinician discretion regarding medical status, appropriateness of participation or concern about intervention adherence

Primary outcomes:
measure: Global cognitive function
timeFrame: up to 2 years
Secondary outcomes:
measure: Episodic Memory
timeFrame: up to 2 years
measure: Executive Function
timeFrame: up to 2 years
measure: Processing Speed
timeFrame: up to 2 years
measure: Clinical Dementia Rating-Sum of Boxes
timeFrame: up to 2 years
measure: Instrumental Activities of Daily Living (IADL)
timeFrame: up to 2 years
measure: Everyday Cognition (ECog)
timeFrame: up to 2 years
measure: Digital Clock Drawing Test (DCTClock)
timeFrame: up to 2 years
measure: Lifestyle Composite
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: Northern California
state: California
city: Chicago
country: United States
facility: Chicagoland--Rush
state: Illinois
city: Downers Grove
country: United States
facility: Chicagoland--Advocate Aurora Health
state: Illinois
city: Winston-Salem
country: United States
facility: North Carolina
state: North Carolina
city: Providence
country: United States
facility: New England--Rhode Island
state: Rhode Island
city: Houston
country: United States
facility: Houston
state: Texas
Study officials:
affiliation: Wake Forest University Health Sciences
name: Laura D Baker, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wake Forest University Health Sciences
name: Mark A Espeland, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Davis
name: Rachel A Whitmer, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Karolinska Institutet
name: Miia Kivipelto, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ngandu T, Lehtisalo J, Solomon A, Levalahti E, Ahtiluoto S, Antikainen R, Backman L, Hanninen T, Jula A, Laatikainen T, Lindstrom J, Mangialasche F, Paajanen T, Pajala S, Peltonen M, Rauramaa R, Stigsdotter-Neely A, Strandberg T, Tuomilehto J, Soininen H, Kivipelto M. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. 2015 Jun 6;385(9984):2255-63. doi: 10.1016/S0140-6736(15)60461-5. Epub 2015 Mar 12.