Alzheimer's DiseaseEarly Phase 1INCREASENCT02849639
The INCREASE Study - Delaying the Onset of Alzheimer's Symptomatic Expression
A Early Phase 1 study testing Medication Therapy Management (MTM) and Scopolamine patch in people with Alzheimer's Disease and Dementia, run by Daniela Moga at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 65 to 101 years
- Conditions the study is for
- Alzheimer's Disease, Dementia
- What is being tested?
- Medication Therapy Management (MTM) and Scopolamine patch
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Apr 2017to 21 Apr 2021
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 to 101 years
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- Myasthenia gravis
- Blockage of the urinary tract.
- Seizures
- Psychosis
Trial locations and contacts
1 site in 1 country.
About this study
Official title: INtervention for Cognitive Reserve Enhancement in Delaying the Onset of Alzheimer's Symptomatic Expression: The INCREASE Study
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.
Read the detailed 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).
- Conditions
- Alzheimer's Disease, Dementia
- Being tested
- Placebo, Medication Therapy Management (MTM), Scopolamine patch
- Keywords
- deprescribing, medication therapy management
- Medical subject headings
- Alzheimer Disease, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboOther
Also called Control
Participants will receive educational materials, but will not receive MTM.
Medication Therapy Management (MTM)Other
Also called Intervention
Participants will receive MTM in addition to the educational materials.
Scopolamine patchDrug
Also called Scopolamine Challenge
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Medication Therapy Management (MTM); Drug: Scopolamine patch |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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 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.
Measured: 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 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
Measured: change from baseline to end of study, an average of 1 year
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 .
Measured: change from baseline to end of study, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2016 (estimated)
- Study start4 Apr 2017
- Primary completion21 Apr 2021
- Study completion21 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Daniela Moga
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor-investigator, Daniela Moga, University of Kentucky
- Investigators
- Daniela Moga, MD, PhD, Principal investigator, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02849639
- Sponsor's protocol ID
- 16-0375-F2L INCREASE
- Other IDs
- 1R01AG054130-01
- Acronym
- INCREASE
- Status last verified
- Jun 2023
- First submitted
- 15 Jul 2016
- Last updated
- 19 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 31888732Moga 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.
PubMed 36281668Smith 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.
PubMed 36894900
Study at a glance
From the registry record, last updated by the sponsor on 19 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- INtervention for Cognitive Reserve Enhancement in Delaying the Onset of Alzheimer's Symptomatic Expression: The INCREASE Study
- ClinicalTrials.gov ID
- NCT02849639
- Acronym / sponsor ID
- INCREASE / 16-0375-F2L INCREASE
- Conditions
- Alzheimer's Disease, Dementia
- Keywords
- deprescribing, medication therapy management
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Daniela MogaUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 4 Apr 2017 (actual)
- Primary completion
- 21 Apr 2021 (actual)
- Study completion
- 21 Apr 2021 (actual)
- First posted
- 29 Jul 2016 (estimated)
- Results
- Posted 22 Aug 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: Placebo, Drug: Scopolamine patchParticipants 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. |
| Medication Therapy Management (MTM) | Active comparator | Other: Medication Therapy Management (MTM), Drug: Scopolamine patchParticipants 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. |
Who may qualify
- Ages
- 65 to 101 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboAlso: ControlParticipants will receive educational materials, but will not receive MTM. | Other | Placebo |
| Medication Therapy Management (MTM)Also: InterventionParticipants will receive MTM in addition to the educational materials. | Other | Medication Therapy Management (MTM) |
| Scopolamine patchAlso: Scopolamine ChallengeAt 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. | Drug | Medication Therapy Management (MTM), Placebo |
Primary outcome
Medication Appropriateness Index
Time frame: change from baseline to end of study, an average of 1 year
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.
Trail Making Test B With the Scopolamine Patch
Time frame: baseline to end of study, an average of 1 year
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.
3 secondary outcomes
Cognitive Reserve: Montreal Cognitive Assessment
Time frame: change from baseline to end of study, an average of 1 year
Cognitive Reserve: California Verbal Learning Test
Time frame: change from baseline to end of study, an average of 1 year
Perceived Health Status
Time frame: change from baseline to end of study, an average of 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jul 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 31888732Moga 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.
- Results publication: PubMed 36281668Moga 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.
- Derived from this study: PubMed 36894900Smith 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniela Moga, MD, PhD principal investigator
University of Kentucky
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Medication Therapy Management (MTM) and Scopolamine patch in people with Alzheimer's Disease and Dementia, run by Daniela Moga at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Medication Appropriateness Index (time frame: change from baseline to end of study, an average of 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02849639, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jul 2023.