A Biomarker Database to Investigate Blood-Based and Digital Biomarkers in Participants Screened for Alzheimer's Disease (Bio-Hermes)

Alzheimer Disease Clinical Trial

Official title:

Development of a Biomarker Database to Investigate Aß, P-tau, and NfL Blood-Based Biomarkers and Digital Biomarkers in Older Participants Screened for Preclinical Alzheimer's Disease (AD), Prodromal AD, or Mild AD

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04733989
• Other study ID #: BIO-HERMES-001
• Status: Completed
• Start date: April 21, 2021
• Est. completion date: November 11, 2022

Study information

• Verified date: February 2023
• Source: GAP Innovations, PBC
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study (Bio-Hermes) is to develop a blood, digital, and brain amyloid PET scan biomarker database that can be used to determine whether a meaningful relationship exists between digital tests, blood amyloid-beta, p-tau, and neurofilament biomarker levels and amyloid-beta levels identified through brain amyloid PET images. Blood collected will also be genetically sequenced to gain insights about genes and brain amyloid. The Bio-Hermes study will include 1,000 volunteers over the age of 60 screened for Preclinical Alzheimer's Disease, Prodromal AD, or Mild Dementia AD, and includes an endpoint enrollment requirement of 200 participants from underrepresented minority populations.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1002
• Est. completion date: November 11, 2022
• Est. primary completion date: November 11, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years to 85 Years

Eligibility

Inclusion Criteria:

Participants must meet all the following criteria for entry into the study:

1. Participants must provide written consent in the IRB-approved informed consent form or have a Legally Authorized Representative (LAR) provide written consent in the IRB-approved consent form on the participant's behalf;

2. Male or female 60 to 85 years of age (inclusive) at the time of consent;

3. Participants must be willing to undergo an amyloid PET scan within 60 days of signing informed consent; or for sites that do not have access to PET imaging, the participant must be willing to undergo a lumbar puncture for cerebrospinal fluid (CSF) collection within 30 days of the coagulation panel;

4. Participants must have a study partner who, in the investigator's judgement, has sufficient and frequent contact (defined as at least 8 hours of contact a week) with the participant and is able to provide accurate information regarding the participant's cognitive and functional abilities;

5. Participants must be willing to comply with all study procedures as outlined in the informed consent, including blood sampling;

6. Fluency in the language of the tests used at the study site;

7. Participants must be willing to be contacted for possible participation in clinical research trials once their participation in this study ends; and

8. Participants must have a Mini-Mental State Exam (MMSE) score of 17 to 30 inclusive at screening; those with a score of 17-19 must have a diagnosis of Probable AD. Exclusion Criteria Participants who meet any of the following criteria will not be eligible for entry into the

study:

1. Participants who, in the opinion of the Site Principal Investigator, have serious or unstable medical conditions that would prohibit their completion of all study procedures and data collection;

2. Participants who have serious or unstable medical conditions that would likely preclude their participation in an interventional research trial;

3. Participants who are unable to undergo amyloid PET due to self-reported pregnancy, sensitivity of ligands being used, poor venous access, contraindication to PET, or planned or recent exposure to ionizing radiation that in combination with the planned administration of amyloid radioligand would result in a cumulative exposure that exceeds recommended local guidelines;

4. Participants who have reported or have a known negative amyloid PET scan in past 12 months;

5. Participants with self-reported, untreated conditions such as vitamin B12 or folate deficiency or bladder infections that in the opinion of the Site Principal Investigator could contribute to cognitive impairment;

6. Participants with history of stroke or seizures within 1 year of the Visit 1 (Screening);

7. Participants with history of cancer within the past 5 years with the exception of non-melanoma skin cancer or prostate cancer in situ;

8. Participants with known or suspected alcohol or drug abuse or dependence within 1 year of the Visit 1 (Screening);

9. Participants who report any current unstable psychiatric symptoms that could interfere with study procedures or impact study data (e.g., uncontrolled depression);

10. Participants who have participated in a clinical trial of any potential disease modifying AD treatment and received active drug within 6 months prior to Visit 1 (Screening);

11. Participants who have completed clinical or observational study procedures (e.g., imaging, cognitive testing) within 3 months of Visit 1 (Screening);

12. Participants who have any neurological disorder affecting the central nervous system, other than AD, that may be contributing to cognitive impairment (e.g., Parkinson's disease, other dementias, multiple concussions or seizures) as deemed significant by the Site Principal Investigator;

13. Participants with a Geriatric Depression Scale (GDS) score greater than or equal to 8 at Visit 1 (Screening);

14. Participants with a RAVLT-Delayed Recall Score of 1.5 standard deviation above the age-adjusted mean;

15. Participants with known history or self-report to be Human Immunodeficiency Virus (HIV) Positive;

16. Participants weighing less than 110 pounds;

17. Participants that have previously been consented to this study unless prior approval was granted by the Sponsor on a case-by-case basis;

18. Participants who are direct employees or family members of direct employees of the participating investigators' sites;

19. Participants who are direct employees of the Sponsor;

20. Participants who, in the opinion of the investigator, are unable to complete cognitive testing due to inadequate visual or auditory acuity;

21. For participants of the RetiSpec retinal substudy only: Those with a known history of ocular diseases (such as retinopathy, age-related macular degeneration, and glaucoma), with the exception of mild to moderate cataracts, and/or vision correction with glasses/contact lenses;

22. For participants undergoing LP: contraindication to lumbar puncture, including coagulopathy, concomitant anticoagulation (except for a platelet inhibitor such as aspirin or clopidogrel), thrombocytopenia, prior lumbar spinal surgery, significant deformity of the lumbosacral region, INR results > 1.3, or other factor that precludes safe LP in the opinion of the Site Principal Investigator.

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer Disease, Early Onset
• Amnesia
• Cognitive Dysfunction
• Memory Disorders
• Memory Impairment
• Memory Loss
• Mild Cognitive Impairment

Intervention

Other:
• Biomarker Data Collection
During this study, a sample of your blood will be collected and you will have a PET scan taken of your brain. Blood sample results will be compared to PET scan pictures to understand how well the markers in the blood predict whether there is amyloid in the brain. Blood samples will also be collected that contain your genes. These genetic samples will also be compared to PET scans to help researchers understand how different people react to medicines and to understand the genetic causes of Alzheimer's disease. Some of the samples will be stored for future analysis.

Locations

Country	Name	City	State
United States	Visionary Investigators Network - Aventura	Aventura	Florida
United States	Great Lakes Clinical Trials	Chicago	Illinois
United States	Visionary Investigators Network - Coral Gables	Coral Gables	Florida
United States	Kerwin Research Center	Dallas	Texas
United States	Kansas University Alzheimer's Disease Center (KUADC)	Fairway	Kansas
United States	Charter Research - Lady Lake	Lady Lake	Florida
United States	JEM	Lake Worth	Florida
United States	ClinCloud	Maitland	Florida
United States	Visionary Investigators Network - South Miami	Miami	Florida
United States	K2	Orlando	Florida
United States	Visionary Investigators Network - Pembroke Pines	Pembroke Pines	Florida
United States	Progressive Medical Research	Port Orange	Florida
United States	El Faro Health and Therapeutics	Rio Grande City	Texas
United States	Velocity Clinical Research - Syracuse	Syracuse	New York
United States	Axiom Clinical Research of Florida	Tampa	Florida
United States	Charter Research - Winter Park	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
GAP Innovations, PBC

Country where clinical trial is conducted

United States, 

References & Publications (16)

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Cahn-Hidalgo D, Estes PW, Benabou R. Validity, reliability, and psychometric properties of a computerized, cognitive assessment test (Cognivue(R)). World J Psychiatry. 2020 Jan 19;10(1):1-11. doi: 10.5498/wjp.v10.i1.1. eCollection 2020 Jan 19. — View Citation

Chetelat G, La Joie R, Villain N, Perrotin A, de La Sayette V, Eustache F, Vandenberghe R. Amyloid imaging in cognitively normal individuals, at-risk populations and preclinical Alzheimer's disease. Neuroimage Clin. 2013 Mar 5;2:356-65. doi: 10.1016/j.nicl.2013.02.006. eCollection 2013. — View Citation

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Howell JC, Watts KD, Parker MW, Wu J, Kollhoff A, Wingo TS, Dorbin CD, Qiu D, Hu WT. Race modifies the relationship between cognition and Alzheimer's disease cerebrospinal fluid biomarkers. Alzheimers Res Ther. 2017 Nov 2;9(1):88. doi: 10.1186/s13195-017-0315-1. — View Citation

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Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, Holtzman DM, Jagust W, Jessen F, Karlawish J, Liu E, Molinuevo JL, Montine T, Phelps C, Rankin KP, Rowe CC, Scheltens P, Siemers E, Snyder HM, Sperling R; Contributors. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018 Apr;14(4):535-562. doi: 10.1016/j.jalz.2018.02.018. — View Citation

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Malzbender K, Lavin-Mena L, Hughes L, Bose N, Goldman D, Patel D. White Paper on Key Barriers to Clinical Trials for Alzheimer's Disease. USC Schaeffer Center for Health Policy & Economics and Gates Ventures. August 2020. https://healthpolicy.usc.edu/wp-content/uploads/2020/08/Key-Barriers-to-Clinical-Trials-for-Alzheimer%E2%80%99s-Disease_FINAL.pdf. Accessed December 01, 2020.

Morris JC, Schindler SE, McCue LM, Moulder KL, Benzinger TLS, Cruchaga C, Fagan AM, Grant E, Gordon BA, Holtzman DM, Xiong C. Assessment of Racial Disparities in Biomarkers for Alzheimer Disease. JAMA Neurol. 2019 Mar 1;76(3):264-273. doi: 10.1001/jamaneurol.2018.4249. — View Citation

Niemantsverdriet E, Valckx S, Bjerke M, Engelborghs S. Alzheimer's disease CSF biomarkers: clinical indications and rational use. Acta Neurol Belg. 2017 Sep;117(3):591-602. doi: 10.1007/s13760-017-0816-5. Epub 2017 Jul 27. — View Citation

O'Bryant SE, Humphreys JD, Smith GE, Ivnik RJ, Graff-Radford NR, Petersen RC, Lucas JA. Detecting dementia with the mini-mental state examination in highly educated individuals. Arch Neurol. 2008 Jul;65(7):963-7. doi: 10.1001/archneur.65.7.963. — View Citation

US Food and Drug Administration. De Novo Classification Request For Cognivue. De Novo Summary (DEN130033). www.accessdata.fda.gov/cdrh_docs/reviews/DEN130033.pdf. Accessed December 7, 2020.

Weiner MW, Veitch DP, Aisen PS, Beckett LA, Cairns NJ, Green RC, Harvey D, Jack CR Jr, Jagust W, Morris JC, Petersen RC, Saykin AJ, Shaw LM, Toga AW, Trojanowski JQ; Alzheimer's Disease Neuroimaging Initiative. Recent publications from the Alzheimer's Disease Neuroimaging Initiative: Reviewing progress toward improved AD clinical trials. Alzheimers Dement. 2017 Apr;13(4):e1-e85. doi: 10.1016/j.jalz.2016.11.007. Epub 2017 Mar 22. — View Citation

Zhang J, Zhou W, Cassidy RM, Su H, Su Y, Zhang X; Alzheimer's Disease Neuroimaging Initiative. Risk factors for amyloid positivity in older people reporting significant memory concern. Compr Psychiatry. 2018 Jan;80:126-131. doi: 10.1016/j.comppsych.2017.09.015. Epub 2017 Oct 6. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measurement of each participant's blood-based biomarker (Beta-Amyloid, Phospho-Tau, Neurofilament Light Chain) levels will be collected through blood sampling.		Through study completion, an average of 1 year
Primary	Measurement of each participant's amyloid levels in the brain will be collected through amyloid PET brain scan imaging.		Through study completion, an average of 1 year