The INCREASE Study - Delaying the Onset of Alzheimer's Symptomatic Expression

Dementia Clinical Trial

— INCREASE  

Official title:

INtervention for Cognitive Reserve Enhancement in Delaying the Onset of Alzheimer's Symptomatic Expression: The INCREASE Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02849639
• Other study ID #: 16-0375-F2L INCREASE
• Secondary ID: 1R01AG054130-01
• Status: Completed
• Phase: Early Phase 1
• Start date: April 4, 2017
• Est. completion date: April 21, 2021

Study information

• Verified date: June 2023
• Source: University of Kentucky
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study will examine the impact on cognitive reserve of a pharmacist-physician patient-centered medication therapy management intervention to address inappropriate medication use as identified by the Beers 2015 list. By bolstering cognitive reserve, this project will directly address the National Alzheimer's Project Act 2015 priorities serving to delay onset of symptoms in preclinical dementia. The results of this study will provide valuable insights on how to expand this intervention to reduce the prevalence and associated healthcare costs of symptomatic Alzheimer's disease.

Description:

This is a 12-month, parallel arm, study to be conducted at the University of Kentucky. The study will involve assessing medication use and identifying any medicines that may be inappropriate for elderly adults.

At the beginning of the study, participants will be asked to undergo one amyloid-PET scan to detect early amyloid plaques in their brain which could increase the risk of Alzheimer's disease in the near future. In addition, at the beginning and end of the study, participants will be asked to use a scopolamine patch. This patch is not being used to prevent motion sickness (as approved by the FDA), but instead is being used to challenge the participant's memory and thinking abilities.

Part of the study includes collecting information regarding participants memory and thinking abilities. Participants will be asked to complete questionnaires as well as memory and thinking tests.

A study doctor will review participants medical history and then perform routine medical (physical and neurological) examinations.

Two of the study visits will be conducted by phone to check up on the participants.

At the beginning, middle, and end of the study, participants will meet with a doctor and pharmacist to review and make any changes deemed appropriate to their current medicines. This will be done in order to try and eliminate medicines that are not recommended for the elderly. These visits are referred to as the Medication Therapy Management (MTM).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: April 21, 2021
• Est. primary completion date: April 21, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years to 101 Years

Eligibility

Inclusion Criteria:

• Non-demented

• No previous reaction or contraindication to scopolamine patch, or medical condition warranting dose adjustment in scopolamine including but not limited to: open angle glaucoma, gastrointestinal or urinary outlet obstructions, seizures, or psychosis.

• No contraindications to Aß-PET scan including hypersensitivity to PET ligand or radiation exposures in the past year that would exceed the acceptable safe annual exposure in combination with the Aß PET

• Medically stable and able to complete all study activities, as determined by the investigator

• Reporting at least one potentially inappropriate medication as listed in the Beers 2015 criteria

• Living in the community

• Willing to participate in this intervention study

Exclusion Criteria:

• Allergy or other know intolerance to scopolamine patches

• Narrow-angle glaucoma

• Difficulty swallowing

• Stomach or bowel problems (e.g., blockage, muscle weakness, ulcerative colitis)

• Bleeding

• Acid reflux disease

• Myasthenia gravis

• Blockage of the urinary tract.

• Seizures

• Psychosis

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease
• Dementia

Intervention

Other:
• Placebo
Participants will receive educational materials, but will not receive MTM.
• Medication Therapy Management (MTM)
Participants will receive MTM in addition to the educational materials.

Drug:
• Scopolamine patch
At the beginning and end of the study, participants will be asked to use a scopolamine patch. This patch is not being used to prevent motion sickness (as approved by the FDA), but instead is being used to challenge the participant's memory and thinking abilities and determine cognitive reserve.

Locations

Country	Name	City	State
United States	University of Kentucky	Lexington	Kentucky

Sponsors (2)

Lead Sponsor	Collaborator
Daniela Moga	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

References & Publications (2)

Moga DC, Abner EL, Schmitt FA, Eckmann L, Huffmyer M, Martinez AI, Beech BF, George R, El Khouli RH, Ali D, Jicha GA. Intervention for Cognitive Reserve Enhancement in Delaying the Onset of Alzheimer's Symptomatic Expression (INCREASE) Study: Results from — View Citation

Moga DC, Beech BF, Abner EL, Schmitt FA, El Khouli RH, Martinez AI, Eckmann L, Huffmyer M, George R, Jicha GA. INtervention for Cognitive Reserve Enhancement in delaying the onset of Alzheimer's Symptomatic Expression (INCREASE), a randomized controlled t — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Medication Appropriateness Index	Change from baseline to end of study. The Medication Appropriateness Index (MAI) rates medications as "appropriate", "marginally appropriate", or "inappropriate" based on ten criteria. All medications reported by study participants were evaluated by the study team and assigned a medication-specific MAI. As an outcome measure, the total MAI was obtained by adding the medication specific MAIs for all medications reported by the participant. Minimum score for one medication is 0 (appropriate) and the maximum is 18 (inappropriate for all criteria). Total MAI depends on the number of medications taken by participant. A decrease in MAI from baseline to end of study indicates improvement in medication appropriateness.	change from baseline to end of study, an average of 1 year
Primary	Trail Making Test B With the Scopolamine Patch	End of study for Trail Making Test B with the scopolamine patch. The mean and standard used to compute the TMTB z-scores were taken from a sample of cognitively intact older adult research volunteers (Weintraub et al. 2009; mean = 90.3, SD = 50) (22). Z-scores were then multiplied by -1 to facilitate interpretation, since higher TMTB scores are worse. For the z-score, we converted time in seconds to units of standard deviations from a mean of 0, where 0 represents the mean performance of cognitively intact (normal) older adult research volunteers enrolled in longitudinal studies at Alzheimer's Disease Research Centers in the United States. Scores that are at least 1.5 standard deviations below the mean are indicative of potential cognitive impairment.	baseline to end of study, an average of 1 year
Secondary	Cognitive Reserve: Montreal Cognitive Assessment	Change from baseline to end of study for Montreal Cognitive Assessment. Z score is based on the NACC cognitively normal population (https://files.alz.washington.edu/documentation/weintraub-2018-v3.pdf), Z score = 0 corresponds mean MoCA score for cognitively normal older adults; higher Z scores are better; typical neuropsych interpretation of z scores is that -1.5 indicates impaired performance on that test.	change from baseline to end of study, an average of 1 year
Secondary	Cognitive Reserve: California Verbal Learning Test	Change from baseline to end of study for California Verbal Learning test. Z scores (higher scores are better; Z score = 0 corresponds mean CVLT score for cognitively normal older adults; typical neuropsych interpretation of z scores is that -1.5 indicates impaired performance on that test) are adjusted for age and sex and are based on the normative population used to develop norms for CVLT-II; "individuals sampled to create the normative data were tested cross-sectionally, demographically matched to the most recent U.S. Censuses, and screened for self-reported neurological, psychiatric, or debilitating medical illnesses." Delis, D. C., Kramer, J. H., Kaplan, E., & Ober, B. A. (1987-2000). California Verbal Learning Test--Second Edition (CVLT -II) [Database record]. APA PsycTests.; https://doi.org/10.1037/t15072-000	change from baseline to end of study, an average of 1 year
Secondary	Perceived Health Status	Change from baseline to end of study for Short Form Health Survey (SF-36). T scores have a mean of 50 and SD of 10; higher scores are better; mean = 50 represents expected mean in general US adult population, with no available clinically relevant thresholds .	change from baseline to end of study, an average of 1 year