Thymus Regeneration, Immunorestoration, and Insulin Mitigation Extension Trial (TRIIM-X)

• ClinicalTrials.gov Identifier: NCT04375657
• Recruitment Status: Recruiting
• First Posted: May 5, 2020
• Last Update Posted: March 1, 2023
• Sponsor: Intervene Immune, Inc.
• Information provided by (Responsible Party): Intervene Immune, Inc.

Tracking Information

• First Submitted Date: May 3, 2020
• First Posted Date: May 5, 2020
• Last Update Posted Date: March 1, 2023
• Actual Study Start Date: November 23, 2020
• Estimated Primary Completion Date: November 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 3, 2020)

• Epigenetic Age [ Time Frame: 12 months ]
  DNA methylation based epigenetic age (GrimAge)
• Thymus Regeneration [ Time Frame: 12 months ]
  Thymic density based on MRI or CT
• Safety and Tolerability [ Time Frame: 12 months ]
  Incidence of treatment-related adverse effects

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 3, 2020)

Immunosenescence [ Time Frame: 12 months ]

Assessment of naive T cells and immune cell function

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

Descriptive Information

• Brief Title: Thymus Regeneration, Immunorestoration, and Insulin Mitigation Extension Trial
• Official Title: Thymus Regeneration, Immunorestoration, and Insulin Mitigation Extension Trial

Brief Summary

The TRIIM-X trial is an expanded pilot clinical study that will evaluate a personalized combination treatment regimen for thymus regeneration. The thymus is a part of the immune system that declines markedly with age, and regenerating it may prevent or reverse key aspects of immunosenescence (immune system aging) and potentially prevent or reverse key parts of the aging process more generally. The study will evaluate biomarkers for epigenetic aging and immunosenescence, as well as evaluate established clinical measures and risk factors for prevention of physical frailty, cancer, cardiovascular disease, diabetes, dementia, and also infectious diseases, including flu and COVID-19.

The study uses multiple agents in combination with personalized doses of recombinant human growth hormone (somatropin), metformin, and DHEA, in a similar manner to how the combination treatment was applied in the earlier TRIIM trial at Stanford, which demonstrated strong statistical significance for the primary efficacy endpoints that will be evaluated in TRIIM-X. Somatropin is approved by the FDA for adult growth hormone deficiency and its use in the study is guided by prior safety data established for that use and also based on safety data available on its prior use in the TRIIM trial and in clinical practice in healthy elderly individuals. There will also be control groups that enable testing of biomarker variability and the contribution of individual medications within the combination treatment.

The objective of the study is to obtain information needed for designing an effective personalized and adaptive treatment regimen for a larger and more diverse study population, and to obtain additional proof of principle for the new use of the medications and biomarkers for preventive medicine. The duration of treatment in the TRIIM-X trial will be 12 months.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

TRIIM-X is an expanded pilot clinical study that will evaluate a personalized combination treatment regimen for thymus regeneration.

Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment

Condition

• Epigenetic Aging
• Immunosenescence

Intervention

• Combination Product: TRIIM Treatment
  Personalized combination of somatropin, metformin, and DHEA
• Combination Product: Active Control
  Metformin and DHEA

Study Arms

• Experimental: TRIIM Treatment
  Intervention: Combination Product: TRIIM Treatment
• Active Comparator: Active Control
  Intervention: Combination Product: Active Control

• Publications *: Fahy GM, Brooke RT, Watson JP, Good Z, Vasanawala SS, Maecker H, Leipold MD, Lin DTS, Kobor MS, Horvath S. Reversal of epigenetic aging and immunosenescent trends in humans. Aging Cell. 2019 Dec;18(6):e13028. doi: 10.1111/acel.13028. Epub 2019 Sep 8.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 3, 2020): 85
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 2024
• Estimated Primary Completion Date: November 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male or female volunteers
• Aged 40 to 80 years, inclusive
• All ethnicities
• Able to participate in 12-month study
• Able to provide informed consent

Exclusion Criteria:

• Malignancies or high risk of malignancy, as suggested by familial risk or personal medical history
• Premenopausal women
• Postmenopausal women on HRT
• IGF-1 levels < 90 ng/ml or >300 ng/ml
• Diagnosed or suspected growth hormone resistance
• Known growth hormone deficiency based on stimulation testing
• Pre-existing carpal tunnel syndrome
• Significant arthritis/arthralgia/joint swelling
• Bradycardia (<55 bpm), significant hypertension (systolic >160 mmHg, or diastolic >90 mmHg) despite treatment, serious angina, or other serious cardiovascular disease or cardiovascular disease risk factors
• Excessive skin growths (e.g., flat warts) without cryosurgical options
• BMI of 35 or greater
• PSA level above the age-adjusted normal range for reasons other than confirmed prostatitis
• Testosterone levels above the upper limit of normal
• Levels of C-reactive protein (CRP) above the upper limit of normal
• Type 1 or pre-existing Type 2 diabetes
• Uncorrected hypothyroidism
• HIV infection
• Allergy or other sensitivity to study medications
• Other unstable medical conditions
• Use of GH within the last 5 years
• Participation in a clinical research trial within 30 days prior to enrollment
• Use of chronic glucocorticoid therapy
• Unwilling to discontinue androgen supplementation if testosterone levels are above the upper limit of normal
• Ongoing treatment with carbonic anhydrase inhibitors
• Ketogenic diet, calorie-restricted diet, or prolonged fasting, without willingness to discontinue these diets or adhere to an alternative diet during the study
• Alcoholism or drug addiction
• Smoking or unwillingness to quit smoking
• Cognitive impairment, illiteracy, inability or unwillingness to give voluntary informed consent

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04375657
• Other Study ID Numbers: TRIIM-X
• 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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Intervene Immune, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Intervene Immune, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Intervene Immune, Inc.
• Verification Date: February 2023