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

NCT02849639 | Completed Early Phase 1 Results DMC FDA Drug

• 2 other identifiers: 16-0375-F2L INCREASE1R01AG054130-01
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Alzheimer's Disease; Dementia

Keywords

deprescribing; medication therapy management

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (3)

• Cognitive Reserve: Montreal Cognitive Assessment

  change from baseline to end of study, an average of 1 year

• Cognitive Reserve: California Verbal Learning Test

  change from baseline to end of study, an average of 1 year

• Perceived Health Status

  change from baseline to end of study, an average of 1 year

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Participants enrolled into this arm will only receive educational materials, but will not receive specific recommendations to make changes to the medications they are taking. Cognitive testing at the beginning and the end of the study will be done with and without a scopolamine patch to reveal cognitive reserve.

Other: Placebo; Drug: Scopolamine patch

Medication Therapy Management (MTM)

ACTIVE COMPARATOR

Participants enrolled into this arm will receive educational materials and will have their medications assessed; recommendations for changes in the medications taken will be made when appropriate. Cognitive testing at the beginning and the end of the study will be done with and without a scopolamine patch to reveal cognitive reserve.

Other: Medication Therapy Management (MTM); Drug: Scopolamine patch

Interventions

Placebo OTHER

Participants will receive educational materials, but will not receive MTM.

Also known as: Control

Placebo

Medication Therapy Management (MTM) OTHER

Participants will receive MTM in addition to the educational materials.

Also known as: Intervention

Medication Therapy Management (MTM)

Scopolamine patch DRUG

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.

Also known as: Scopolamine Challenge

Medication Therapy Management (MTM); Placebo

Eligibility Criteria

• Age: 65 Years - 101 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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 Aβ-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 Aβ 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Daniela Moga: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Related Publications (3)

• 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 trial: rationale, study design, and protocol. Trials. 2019 Dec 30;20(1):806. doi: 10.1186/s13063-019-3993-0.

  PMID: 31888732 RESULT

• 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 a Randomized Controlled Study of Medication Therapy Management Targeting a Delay in Prodromal Dementia Symptom Progression. J Prev Alzheimers Dis. 2022;9(4):646-654. doi: 10.14283/jpad.2022.55.

  PMID: 36281668 RESULT

• Smith NI, Martinez AI, Huffmyer M, Eckmann L, George R, Abner EL, Jicha GA, Moga DC. Acceptability of patient-centered, multi-disciplinary medication therapy management recommendations: results from the INCREASE randomized study. BMC Geriatr. 2023 Mar 10;23(1):137. doi: 10.1186/s12877-023-03876-4.

  PMID: 36894900 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Dementia

Interventions

Medication Therapy Management; Methods

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pharmaceutical Services; Health Services; Health Care Facilities Workforce and Services; Medicare Part D; Insurance, Pharmaceutical Services; Insurance, Health; Insurance; Financing, Organized; Economics; Health Care Economics and Organizations; Medicare; Patient Care Management; Health Services Administration; Investigative Techniques

Results Point of Contact

• Title: Daniela C Moga MD PhD, Associate Professor
• Organization: University of Kentucky

daniela.moga@uky.edu

859-323-9682

Study Officials

• Daniela Moga, MD, PhD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor/PI

Study Record Dates

• First Submitted: July 15, 2016
• First Posted: July 29, 2016
• Study Start: April 4, 2017
• Primary Completion: April 21, 2021
• Study Completion: April 21, 2021
• Last Updated: July 19, 2023
• Results First Posted: August 22, 2022

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)