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Reversing Epigenetic & Other Markers of Senescence by Transfusing Young Plasma To Older Human Subjects (RESET-YOUTH)

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ClinicalTrials.gov Identifier: NCT03353597
Recruitment Status : Not yet recruiting
First Posted : November 27, 2017
Last Update Posted : January 17, 2018
Sponsor:
Information provided by (Responsible Party):
Chandra Duggirala, Fountain Labs, Inc.

Tracking Information
First Submitted Date  ICMJE November 7, 2017
First Posted Date  ICMJE November 27, 2017
Last Update Posted Date January 17, 2018
Estimated Study Start Date  ICMJE May 15, 2018
Estimated Primary Completion Date June 15, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 24, 2017)
Biological age as assessed by DNA methylation levels, to calculate the Epigenetic age. [ Time Frame: Baseline to end of Month 9. ]
The "epigenetic clock," as assessed by DNA methylation levels, which has been shown to be highly correlated with biologic age, longevity and is an independent predictor of mortality.
Original Primary Outcome Measures  ICMJE
 (submitted: November 21, 2017)
Biological age as assessed by DNA methylation levels, to calculate the Epigenetic age. [ Time Frame: Baseline to end of Month 9. ]
The "epigenetic clock," as assessed by DNA methylation levels, which has been shown to be highly correlated with biologic age, longevity and is an independant predictor of mortality.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 24, 2017)
  • Mental (Cognitive) Function [ Time Frame: Baseline and Month 9 ]
    Executive functioning, as measured by the California Stroop test
  • Lung (Pulmonary) Function [ Time Frame: Baseline and Month 9 ]
    FEV1 (Forced Expiratory Volume during the first second), and Peak Expiratory Flow
  • Kidney (Renal) Function [ Time Frame: Baseline and Month 9 ]
    Twenty-four hour urine collections will be performed by patients at Baseline and at Month 9. Creatinine Clearance, a measure of Renal function will be determined by calculating the glomerular filtration rate (GFR), which is the sum of filtration rates in all functioning nephrons.
  • Muscle Strength [ Time Frame: Baseline and Month 9 ]
    Unilateral Maximal Voluntary Isometric and Concentric Strength
  • Telomere Length [ Time Frame: Baseline and Month 9 ]
    A telomere is a region of repetitive nucleotide sequences at each end of a chromosome, which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes. Telomere shortening is associated with aging, mortality and aging-related diseases. Average telomere length will be measured in white blood cells by real time PCR technique.
  • Testosterone [ Time Frame: Baseline and Month 9 ]
    Serum free and total Testosterone levels
  • Estrogen [ Time Frame: Baseline and Month 9 ]
    Serum Estrogen levels
  • DHEAS [ Time Frame: Baseline and Month 9 ]
    Dehydroepiandrosterone is an endogenous steroid hormone that has a role in the synthesis of sex steroids (androgens and estrogens), as well as neurotrophic and other effects
  • IGF-1 [ Time Frame: Baseline and Month 9 ]
    Insulin Like Growth Factor -1(IGF-1) declines continuously with aging in adults, and has been shown to mediate a number of pathways that are associated with longevity.
  • High Sensitivity C-Reactive Protein [ Time Frame: Baseline and Month 9 ]
    C-Reactive Protein is a blood protein that is a marker of inflammation. Studies have suggested that a persistent level of inflammation plays a major role in cardiovascular and other degenerative and aging related diseases.
  • P16INK4a (A marker of cellular aging) [ Time Frame: Baseline and Month 9 ]
    The cyclin- dependent kinase inhibitor CDKN2A, commonly referred to as p16INK4a or p16, has been established as a general marker of cellular senescence or aging. The expression of p16INK4a has been shown to increase exponentially with chronologic age. P16-INK4a is performed on a small specimen of blood drawn from the subjects, as well as from skin biopsy samples.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 21, 2017)
  • Mental (Cognitive) Function [ Time Frame: Baseline and Month 9 ]
    Executive functioning, as measured by the California Stroop test
  • Lung (Pulmonary) Function [ Time Frame: Baseline and Month 9 ]
    FEV1 (Forced Expiratory Volume during the first second), and Peak Expiratory Flow
  • Kidney (Renal) Function [ Time Frame: Baseline and Month 9 ]
    Twenty-four hour urine collections will be performed by patients at Baseline and at Month 9. Creatinine Clearance, a measure of Renal function will be determined by calculating the glomerular filtration rate (GFR), which is the sum of filtration rates in all functioning nephrons.
  • Muscle Strength [ Time Frame: Baseline and Month 9 ]
    Unilateral Maximal Voluntary Isometric and Concentric Strength
  • Telomere Length [ Time Frame: Baseline and Month 9 ]
    A telomere is a region of repetitive nucleotide sequences at each end of a chromosome, which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes. Telomere shortening is associated with aging, mortality and aging-related diseases. Average telomere length will be measured in white blood cells by qPCR technique.
  • Testosterone [ Time Frame: Baseline and Month 9 ]
    Serum free and total Testosterone levels
  • Estrogen [ Time Frame: Baseline and Month 9 ]
    Serum Estrogen levels
  • DHEAS [ Time Frame: Baseline and Month 9 ]
    Dehydroepiandrosterone is an endogenous steroid hormone that has a role in the synthesis of sex steroids (androgens and estrogens), as well as neurotrophic and other effects
  • IGF-1 [ Time Frame: Baseline and Month 9 ]
    Insulin Like Growth Factor -1(IGF-1) declines continuously with aging in adults, and has been shown to mediate a number of pathways that are associated with longevity.
  • High Sensitivity C-Reactive Protein [ Time Frame: Baseline and Month 9 ]
    CRP is a blood protein that is a marker of inflammation. Studies have suggested that a persistent level of inflammation plays a major role in cardiovascular and other degenerative and aging related diseases.
  • P16INK4a (A marker of cellular aging) [ Time Frame: Baseline and Month 9 ]
    The cyclin- dependent kinase inhibitor CDKN2A, commonly referred to as p16INK4a or p16, has been established as a general marker of cellular senescence or aging. The expression of p16INK4a has been shown to increase exponentially with chronologic age. P16-INK4a is performed on a small specimen of blood drawn from the subjects, as well as from skin biopsy samples.
Current Other Pre-specified Outcome Measures
 (submitted: November 24, 2017)
Exploratory biomarkers [ Time Frame: Baseline,1,2,3,4,5,6, and 9 months. ]
Blood, and urine, proteomic signatures of aging, including Interleukin-6, Tumor Necrosis Factor Alpha, Tissue Inhibitor of Metallo Proteinases-2, Transforming Growth Factor-Beta, and Mechanistic Target of Rapamycin (mTOR) levels, that are associated with various cellular, genetic and physiological mechanisms of aging will be measured at Baseline, 1,2,3,4,5,6, and 9 months.
Original Other Pre-specified Outcome Measures
 (submitted: November 21, 2017)
Exploratory biomarkers [ Time Frame: Baseline,1,2,3,4,5,6, and 9 months. ]
Blood, and urine, proteomic signatures of aging, including IL-6, TNF Alpha, TIMP-2, TGF-Beta, and mTOR levels, that are associated with various cellular, genetic and physiological mechanisms of aging will be measured at Baseline, 1,2,3,4,5,6, and 9 months.
 
Descriptive Information
Brief Title  ICMJE Reversing Epigenetic & Other Markers of Senescence by Transfusing Young Plasma To Older Human Subjects
Official Title  ICMJE Reversing Epigenetic & Other Markers of Senescence by Transfusing Young Plasma To Older Human Subjects
Brief Summary This trial is designed to study the effects of monthly transfusions of young healthy male donor plasma on biological age as assessed by DNA methylation levels, and changes in cognitive, renal, and pulmonary function, muscle strength, telomere length, testosterone, estrogen, DHEAS, IGF-1, high resolution C-Reactive protein, and expression of P16INK4a in peripheral blood T lymphocytes and skin biopsies.
Detailed Description Aging is a process for which there is no cure. Plasma transfusions, based on extensive animal studies, have the potential to reverse many, systemic age-related changes in the human body as well as age related chronic diseases. This is a non-randomized, uncontrolled phase I/II study to study the effects of monthly transfusions of young healthy male donor plasma on biological age as assessed by DNA methylation levels, and changes in cognitive, renal, and pulmonary function, muscle strength, telomere length, testosterone, estrogen, DHEAS, IGF-1, high resolution C-Reactive protein, and expression of p16INK4a in peripheral blood T lymphocytes and skin biopsies. To determine the safety and tolerability of monthly, 2-unit transfusions of young (<25 years of age) healthy male donor plasma for 6 months in patients older then 40 years of age.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Aging
Intervention  ICMJE Biological: Plasma Transfusion
All subjects will receive monthly, 2-unit transfusions of young healthy male donor plasma for total of 6 treatments. The plasma will be administered at a transfusion services facility in a manner consistent with generally accepted and standard guidelines for plasma transfusions.
Study Arms  ICMJE Experimental: Plasma Transfusion
Plasma Transfusions with 2 units of plasma per dose, for a total of 6 doses
Intervention: Biological: Plasma Transfusion
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: November 21, 2017)
2120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 15, 2022
Estimated Primary Completion Date June 15, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age > 40.
  • Stable medications for 2 months prior to Screening.
  • Signed and dated written informed consent obtained from the subject in accordance with local Institutional Review Board regulations.
  • Males and all Women of Child Bearing Potential agree to abstain from sex or use an adequate method of contraception for the duration of the study and for 30 days after the last dose of study drug. Adequate contraceptive methods include those with a low failure rate, i.e., less than 1% per year, when used consistently and correctly), and , a woman who has been surgically sterilized or who has been in a state of amenorrhea.

Exclusion Criteria:

  • Dementia of any etiology.
  • Any medical condition other than dementia that could account for cognitive deficits (e.g., active seizure disorder, stroke, Central Nervous System diseases);
  • History of significant cardiovascular, hematologic, renal, or advanced hepatic disease (or laboratory evidence thereof);
  • History of major psychiatric illness or untreated depression;
  • Neutrophil count <1,500/mm3, platelets <100,000/mm3, serum creatinine >1.5x upper limit of normal (ULN), total bilirubin >1.5 x ULN, Alanine Transaminase >3 x ULN, Aspartate Transaminase >3 x ULN, or International Normalized Ratio (INR) >1.2 at Screening evaluations;
  • Evidence of any clinically significant findings on Screening or baseline evaluations which, in the opinion of the Investigator would pose a safety risk or interfere with appropriate interpretation of study data;
  • Current or recent history (within four weeks prior to Screening) of a clinically significant bacterial, fungal, or mycobacterial infection;
  • Current clinically significant viral infection;
  • Major surgery within four weeks prior to Screening;
  • Any contraindication to monthly plasma transfusions, including but not limited to:
  • History of significant transfusion complications;
  • Compatible plasma units not available;
  • Prior intolerance to intravenous (IV) fluids;
  • Immunoglobulin A deficiency by history or laboratory evidence at Screening;
  • Bleeding;
  • Any concurrent use of an anti-coagulant therapy.
  • Daily administration of Aspirin 81mg will be allowed as long as the dose is stable for 30 days prior to Screening. Anti-platelet drugs are acceptable.
  • Treatment with another investigational drug or participation in another interventional clinical trial within 3 months of Screening;
  • Treatment with any human blood product, including IV immunoglobulin, during the 6 months prior to Screening or during the trial;
  • Pregnant or lactating;
  • Positive pregnancy test at Screening or Baseline (Day 1);
  • Cancer within 5 years of Screening, except for nonmetastatic skin cancer or non-metastatic prostate cancer not expected to cause significant morbidity or mortality within one year of Baseline.
  • AB blood type.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Chandra s Duggirala, MBBS, MD 815-793-1273 cduggi@gmail.com
Contact: Chandra S Duggirala 9252334334 cduggi@gmail.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03353597
Other Study ID Numbers  ICMJE FFP-1
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Chandra Duggirala, Fountain Labs, Inc.
Study Sponsor  ICMJE Chandra Duggirala
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Chandra s duggirala Fountain Labs, Inc.
PRS Account Fountain Labs, Inc.
Verification Date January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP