CClinicalTrials.gg
Status unknownNCT03353597RESET-YOUTHUpdated Jan 17, 2018

Reversing Epigenetic & Other Markers of Senescence by Transfusing Young Plasma To Older Human Subjects

A Phase 1/2 interventional study of Plasma Transfusion in Aging, sponsored by Chandra Duggirala. Status unknown at 1 site in United States. Open to participants aged 40 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-01-17.

Sponsored by Chandra Duggirala · Phase 1/2, Interventional, and Treatment

The sponsor has not verified this record recently (last verified Jan 2018), so the status shown — last known as Not yet recruiting — may be out of date.
Phase
Phase 1/2
Study type
Interventional
Enrollment
2,120
Allocation
Not applicable
Ages
40 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Aging
03

Who can participate

Ages eligible
40 Years and older
Sexes eligible
All
Accepts healthy volunteers
Yes

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

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.
04

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
2,120 participants (estimated)

Study arms

  • Experimental
    Plasma Transfusion

    Plasma Transfusions with 2 units of plasma per dose, for a total of 6 doses

    Biological: Plasma Transfusion

Interventions

  • BiologicalPlasma 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.

05

What researchers measure

Primary outcomes

  1. Biological age as assessed by DNA methylation levels, to calculate the Epigenetic age.

    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.

    Time frame: Baseline to end of Month 9.

Secondary outcomes

  1. Mental (Cognitive) Function

    Executive functioning, as measured by the California Stroop test

    Time frame: Baseline and Month 9

  2. Lung (Pulmonary) Function

    FEV1 (Forced Expiratory Volume during the first second), and Peak Expiratory Flow

    Time frame: Baseline and Month 9

  3. Kidney (Renal) Function

    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.

    Time frame: Baseline and Month 9

  4. Muscle Strength

    Unilateral Maximal Voluntary Isometric and Concentric Strength

    Time frame: Baseline and Month 9

  5. Telomere Length

    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.

    Time frame: Baseline and Month 9

  6. Testosterone

    Serum free and total Testosterone levels

    Time frame: Baseline and Month 9

  7. Estrogen

    Serum Estrogen levels

    Time frame: Baseline and Month 9

  8. DHEAS

    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

    Time frame: Baseline and Month 9

  9. IGF-1

    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.

    Time frame: Baseline and Month 9

  10. High Sensitivity C-Reactive Protein

    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.

    Time frame: Baseline and Month 9

  11. P16INK4a (A marker of cellular aging)

    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.

    Time frame: Baseline and Month 9

Other outcomes

  1. Exploratory biomarkers

    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.

    Time frame: Baseline,1,2,3,4,5,6, and 9 months.

06

Study locations

1 site
  • The Infusion Center & Clinic
    San Mateo, California 94401, United States
    • Janeen Bc · Contact · 650-348-6011
    • S · Contact
07

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Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03353597
Lead sponsor
Chandra Duggirala
Responsible party
Chandra Duggirala (Principal Investigator, Fountain Labs, Inc.) — Sponsor-investigator
First posted
Nov 27, 2017
Start date
May 15, 2018 (estimated)
Primary completion
Jun 15, 2020 (estimated)
Completion
Dec 15, 2022 (estimated)
Last update
Jan 17, 2018

Study contacts

Chandra s Duggirala, MBBS, MD
Contact
cduggi@gmail.com
815-793-1273
Chandra S Duggirala
Contact
cduggi@gmail.com
9252334334
Chandra s duggirala
principal investigator · Fountain Labs, Inc.

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is status unknown, as verified in Jan 2018. You cannot join it, but the record below documents what was studied.

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