PhosphoRus, Proton Imaging and Amyloid BuRdEn (PREPARE) ON AMYLOID BURDEN AND COGNITION (PREPARE)

• ClinicalTrials.gov Identifier: NCT03999879
• Recruitment Status: Recruiting
• First Posted: June 27, 2019
• Last Update Posted: August 5, 2022
• Sponsor: NYU Langone Health
• Information provided by (Responsible Party): NYU Langone Health

Tracking Information

• First Submitted Date: June 25, 2019
• First Posted Date: June 27, 2019
• Last Update Posted Date: August 5, 2022
• Actual Study Start Date: May 1, 2019
• Estimated Primary Completion Date: February 28, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 25, 2019)

(PCr)-to-ATP ratio levels [ Time Frame: 1 Month ]

These 31P-MRSI data will differentiate PiB+ aMCI individuals from PiB+ NL individuals.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: PhosphoRus, Proton Imaging and Amyloid BuRdEn (PREPARE) ON AMYLOID BURDEN AND COGNITION
• Official Title: Neuroenergetic Adaptations in Alzheimer's Disease: Implications on Amyloid Burden and Cognition.
• Brief Summary: Normal cells primarily produce energy with the help of the "mitochondria". These "small organs" are also called the "powerhouses of the cell" turn the sugars, fats and proteins that is eaten into forms of chemical energy that the body can use to carry on living. This process is called oxidative phosphorylation. In addition to the help from the mitochondria and oxidative phosphorylation, most cells can produce energy by lactic acid fermentation. This process is less energy efficient but faster and used by the brain, muscle or other organs under specific circumstances and energy demands, even in the presence of abundant oxygen. It is also called aerobic glycolysis. Aerobic glycolysis and oxidative phosphorylation are the two major mechanisms involved in brain energetics.
• Detailed Description: The consequences of Alzheimer's disease (AD) (deposition of amyloid plaques and neurofibrillary tangles) are known. The cause of these deposition of proteins is not. Some scientist argue that an increase in oxidative phosphorylation activity and a lack of ability to shift to aerobic glycolysis are the underlying source of these changes. The purpose of this study is to test whether there is a correlation between neuroenergetic levels of aerobic glycolysis/oxidative phosphorylation and risk for Alzheimer's disease. The study will examine these neuroenergetic adaptations in a group of 15 elderly participants (age range: 70-85 y/o) with amnestic mild cognitive impairment (aMCI) and 30 cognitively normal controls (NL). Multimodal (MR/PET) and multinuclear (31P/1H) neuroimaging will allow us to gain access to a uniquely comprehensive and highly consistent view of neuroenergetic adaptations in both the clinical and preclinical stages of Alzheimer's disease.
• Study Type: Observational
• Study Design: Observational Model: Other; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: Adults (male and female) aged >70 years in overall excellent health with normal cognition (CDR=0), and at least high school graduate level education.
• Condition: Alzheimer Disease

Intervention

• Diagnostic Test: Measure of OxPhos upregulation
  OxPhos upregulation [i.e., lower phosphocreatine (PCr)-to-ATP ratio levels] in the PET AG mask. PIB+ NL subjects will show OxPhos downregulation (i.e. increased PCr/ATP ratio that indicate the presence of metabolically inert PCr that cannot be used as ATP) when compared to PIB- NL subjects in the PETAG mask
• Diagnostic Test: lactate (measured with 1H-MRSI)
  PIB+ NL subjects will show increased levels of lactate (measured with 1H-MRSI) when compared to PIB- NL subjects in the PETAG mask.

Study Groups/Cohorts

• Cognitively Normal
  having 30 participants with normal cognition
  Interventions:

  • Diagnostic Test: Measure of OxPhos upregulation
  • Diagnostic Test: lactate (measured with 1H-MRSI)
• Amnesic MCI
  aMCI Group having 15 participants with a CDR of 0.5-1 and a Mini-Mental State Examination (MMSE) of 20-25.
  Interventions:

  • Diagnostic Test: Measure of OxPhos upregulation
  • Diagnostic Test: lactate (measured with 1H-MRSI)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 9, 2022): 17
• Original Estimated Enrollment (submitted: June 25, 2019): 45
• Estimated Study Completion Date: February 28, 2023
• Estimated Primary Completion Date: February 28, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• NL Group: Adults (male and female) aged >70 years in overall excellent health with normal cognition (CDR=0), and at least high school graduate level education.
• aMCI Group: Adults (male and female) aged >70 years, Clinical Dementia Rating (CDR)= 0.5 - 1 and Mini-Mental State Examination (MMSE): 20-25
• English as first language or demonstrated proficiency in English for non-native speakers

Exclusion Criteria:

• Any tumor, stroke, or trauma that would result in abnormal radiological findings History of bipolar disorder, schizophrenia, intellectual disability or substance abuse MRI scanner contraindications

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 70 Years to 85 Years (Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Katherine Medina; 212-263-5053; katherine.medina@nyulangone.org

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03999879
• Other Study ID Numbers: 18-01919
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: NYU Langone Health
• Original Responsible Party: Same as current
• Current Study Sponsor: NYU Langone Health
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Ryan Brown, MD; New York Langone Medical Center

• PRS Account: NYU Langone Health
• Verification Date: August 2022