Baltimore, Maryland 21224


Purpose:

Background: - Biomarkers are substances in people s blood and tissues. They help researchers understand diseases and signs of aging. Scientists want to do more research on biomarkers to find ways to improve quality of life in old age. Objective: - To learn more about biomarkers and their relationship to aging. Eligibility: - Adults at least 20 years old who weigh at least 110 pounds and have a body mass index below 30. They must agree that their genetic samples can be collected, studied, and stored. Design: - Participants will be screened with medical history, physical exam, and blood and urine tests. They will have heart tests and nurse will assess their veins. They will fill out a questionnaire. - Participants will have a 2-day baseline visit. Then they will return every 2 years for up to 10 years. These follow-up visits will repeat the baseline visit: - Repeat of screening procedures. - Physical performance tests like balance and walking tests. - Leg and grip strength tests. - Health and mental state questions. - Memory and problem solving tests. - Cytapheresis. Blood will be removed through a needle in the vein of one arm and run through a machine. The blood will be returned through a needle in a vein of the other arm. - Visits may also include: - Magnetic resonance imaging scans. Participants will lie on a table that slides in and out of a machine that takes pictures. - Diabetes test. After fasting, participants will drink a sweet drink and give blood. - Breathing and walking tests. - Wearing a device that record physical activity. - Scan of the abdomen and the right leg. - A small amount of muscle tissue and/or skin removed.


Study summary:

Under the assumption that aging is caused by dysfunction of specific biological mechanisms, it is reasonable to hypothesize that slowing aging should delay the onset of chronic diseases that typically affect older persons and improve their longevity and quality of life. Indeed, there is emerging evidence that factors associated with premature mortality are also involved in multiple pathologic conditions typical of aging. Scientists have suggested that these factors are genetic in nature and involve variations in the genetic code sequence. Contrary to this view, genetic approaches to study of aging have had limited success and it has been argued that the study of aging and longevity requires a more comprehensive analysis that includes non-genetic biomarkers such as epigenetic, gene expression and protein biomarkers. This is because these non-genetic biomarkers reflect the interaction between genetic variation and environmental/behavioral factors. A major limitation in this approach to date is that most studies of epigenetic, gene expression and protein biomarkers rely on blood specimens, which may not recapitulate the biology of other tissues. In addition, although all cell types from the same person have exactly the same genetic code; information on epigenetic modifications, RNAm, and protein expression likely differ across cell types and at different points in time. Thus, global measures of these biomarkers in specific cell types can be affected by percentages of these cell types in the blood, and it is well know that such percentages change with aging and chronic diseases. To overcome the limitations described above, we plan to use cytapheresis to collect large number of PBMCs in a group of healthy individuals dispersed over a wide age-range. The collection of large number of PBMCs is essential to obtain a sufficient number of cells for each cell type to support measurements of the biomarkers of interest. The information collected will be used to identify biomarkers that change with aging in individuals who are initially healthy, independent of changes in specific PBMCs cell types. We will also develop a statistical model that can be used by other studies of biomarkers to adjust their analysis for PBMCs cell type composition without having to perform complex and expensive measures, such as flow cytometry. The data collected in PBMCs will be compared to similar biomarker data obtained from muscle and skin biopsies to understand to what extent biomarkers measured in the blood recapitulate similar changes that occur in different human tissues. Finally, once methodological limitations of measuring biomarkers in the blood have been addressed, we plan to assess the relationship of biomarkers assessed in specific circulating cell types, in the whole blood and in muscle and skin biopsies to physiological measures that typically change with aging, including measures of body composition (anthropometrics, CT scan and MRI), energetics (spirometry at rest and during different degrees of exercise intensity), homeostatic equilibrium (hormones and inflammatory markers), neurological function (neurocognitive testing, brain MRI, nerve conduction studies). At the first follow-up, Year 2 (and every four years after it) we will focus on in depth characterization of phenotypes that are relevant for aging. This strategy reduces the burden to participants but still allows delineating trajectories of essential variables and relate them longitudinally.The final goal is to develop new hypotheses about the biological nature of the aging process and how aging is associated with decline of physical and cognitive function.


Criteria:

- Since the study of gene expression and epigenetic regulation are essential aims of GESTALT, all participants are required to consent to DNA/RNA testing and storage at the Screening Visit and all subsequent Follow-up Visits. Participants that refuse genetic testing and storage will not be eligible to participate or to continue to participate in the study. The criteria below pertain only to the Screening and Baseline Visits, except where otherwise noted. If any of the conditions develop while the participant is in the study, the participant remains in the study. In particular, participants who develop cognitive and motor problems from medical conditions such as stroke or Parkinson s disease are retained in the study, although they are excluded from specific testing in which their underlying health condition is an exclusion criterion. Participants that develop more severe cognitive problems and are diagnosed with dementia, will no longer be able to participate in the study. Inclusion Criteria: - Age greater than or equal to 20 years of age. - Are willing to return every 2 years for study visit procedures. - Agree to genetic (DNA/RNA) sample collection, analysis and storage. - Have good venous access for cytapheresis and are in good health as determined by the Apheresis Health History Questionnaire and are found eligible for apheresis (Apheresis Eligibility form). - Weigh greater than or equal to 110lbs and a body mass index (BMI) < 30. - Do not have established genetic diseases such as sickle cell, hemochromatosis (iron overload), cystic fibrosis or Ehlers-Danlos syndrome (connective tissue disorder). - Do not have autoimmune diseases such as Hashimoto s thyroiditis, Myasthenia Gravis or Rheumatoid arthritis. - Report that they are able to perform daily self- care without assistance. - Report that they able to walk independently for at least 400 meters without assistance and without developing severe symptoms. - Report they are able to perform normal activities of daily living without shortness of breath (walking or climbing stairs) or other severe symptoms. Do not have cognitive impairment based on mental status screening tests (MMSE < 26 or Blessed Mental > 3. - Do not have a history of cardiovascular disease or cerebrovascular disease including angina (requiring treatment), myocardial infarction, congestive heart failure, uncontrolled hypertension, pacemaker, stroke or transient ischemic attacks (TIA). - Do not have a history of diabetes (requiring any medical treatment other than diet and exercise) and their fasting Glucose is <126 mg/dL. - Do not have active (any activity in the last 10 years) cancer, except for locally limited basal cell cancer. - Do not have clinically significant hormonal dysfunction (Self-reported or laboratory values out of range. Mild hypothyroidism in participants over 60 is not considered exclusion). - Do not have a history of neurological diseases or birth defects (other than minor anatomical abnormalities, which do not affect physical and/or cognitive function). - Do not have a history of kidney or liver disease (associated with reduced kidney or liver function). - Do not have a history of severe gastrointestinal (G.I.) diseases, with symptoms or requiring chronic treatment such as gastroesphageal reflux disease (GERD), Crohn s disease or ulcerative colitis. - Do not have a history of severe pulmonary disease such as chronic obstructive pulmonary disease (COPD) or asthma requiring continuous medication use. - Do not have muscle-skeletal conditions due to diseases or traumas (that cause pathological weakness and/or chronic pain). - Do not have a history of severe psychiatric conditions associated with behavioral problems or requiring chronic medical treatment. - Do not have any medical condition that requires absolute and continuous need for long term treatment with antibiotics, corticosteroids, immunosuppressors, H2 blockers and/or proton pump inhibitors, or pain medications.-Do not have a medical condition that requires the use of chronic anticoagulant medication use such as Coumadin, heparin or antiplatelet agents other than low dose aspirin. - Do not have important sensory deficits (legally blind and/or any condition that precludes the participant from being tested with standard neuropsychological tests or providing informed consent). - Are able to read and speak English. - Are able to understand the study risks and procedures, and consent to participate in the study. - Not currently pregnant or a nursing mother. - Do not currently smoke and have not smoked in the past 3 months. - Veins are adequate for cytapheresis - No current illness that as judged by the study physician substantially increases the risks associated with cytapheresis (active infections, allergies, etc.). - No history of allergy to acid- citrate- dextrose (ACD) anticoagulant. - No history of an active bleeding disorder such as hemophilia or Von Willebrand disease. - No history of seizures within the last 3 months. - No history of Lyme disease, unless six weeks post treatment and no new symptoms, of Chagas disease, Babesiosis, or Leishmanias. - Are not claustrophobic and are eligible to perform MRI as per the MRI eligibility form - Do not have hip or knee replacements or other medical conditions that prevent MRI research scans from being performed Participant Exclusion Criteria These criteria pertain to the Screening and Baseline Visits. If conditions considered as exclusion criteria for study entry develop any time after the baseline evaluation, the participant remains in the study. Exclusion Criteria: - HIV virus infection. - Hepatitis B or C. - Active syphilis, gonorrhea or TB requiring treatment. - WBC <3,000 or > 12,000/mcrL. - Platelets < 100,000 or >600,000 /mcrL. - Hemoglobin < 11.0 g/dL in women and < 12.0 in men. - Creatinine >1.6 mg/dl or calculated creatinine clearance < 50 cc/min. - Bilirubin > 1.5 mg/dl (unless higher levels can be ascribed to Gilbert s disease. - ALT, AST or alkaline phosphatase twice the normal serum concentration. - Corrected calcium < 8.5 or > 10.7 mg/dl. - Albumin < 3.1 g/dl. - Positive Urine Drug Screen (unless taking prescribed medication and at the discretion of the PI). Furthermore, if the participant is found eligible at screening and baseline but fails a urine drug screen (unless taking prescribed medication and at the discretion of the PI). at any of the subsequent (follow-up) visits, the participant will be asked to return in about 30 days to repeat the test and if positive, will no longer be eligible to participate in the study. If female and found to be pregnant during pregnancy screening at any visit, the participant will need to reschedule their visit for when they are 3 months postpartum and/or post breastfeeding. Justification for Exclusion of Women, Minorities, and Children (Special Populations) Exclusion of Women: Not Applicable - Pregnancy: Women of child bearing age who become pregnant during the study will be deferred from a study visit until they are no longer pregnant and breastfeeding (3 months post pregnancy and/or breastfeeding). - Exclusion of Children: Participants under the age of 20 years old will not be allowed to participate in GESTALT because GESTALT is a study on the aging of adults and does not include the developmental growth period of children. - Exclusion of Non-English Speaking Subjects: Due to the complexity of testing/ procedures and extensive cognitive testing protocols, consents, instructions and questionnaires are provided in English. Therefore, all participants must be able to able to read and speak English. To date, the NIA located in Baltimore has not had non-English speaking participants interested in participating in studies. In regards to this study, should this occur in the future, the Principal Investigator, in conjunction with the requirements of SOP 12 Requirements of Informed Consent, and more specifically 12.9.1 Non-English Speaking Subjects will be used to determine if changes related to recruitment and enrollment of non-English speaking participants is needed.


NCT ID:

NCT02339012


Primary Contact:

Principal Investigator
Luigi Ferrucci, M.D.
National Institute on Aging (NIA)

Luigi Ferrucci, M.D.
Phone: (410) 558-8110
Email: ferruccilu@grc.nia.nih.gov


Backup Contact:

N/A


Location Contact:

Baltimore, Maryland 21224
United States

NIA Studies Recruitment
Phone: 410-350-3941
Email: niastudiesrecruitment@mail.nih.gov

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: November 21, 2017

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