AgingPhase 2NCT02874924
Effect of mTOR Inhibition and Other Metabolism Modulating Interventions on the Elderly
A Phase 2 study testing Rapamycin in people with Aging, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
Trial summary
The ability to mount an effective immune response declines with age, leaving the elderly increasingly susceptible to infectious diseases and cancer. Rapamycin, an FDA approved drug to prevent transplant rejection, increases the lifespan and healthspan of mice and ameliorates age-related declines in immune… Read more about this study
- Who is it for?
- Ages 70 to 95 yearsHealthy volunteers can take part
- Conditions the study is for
- Aging
- What is being tested?
- Rapamycin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2016to Sep 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 70 to 95 years
- All sexes
- Healthy volunteers accepted
- Older adult
Who may be able to join
- participants will be in good health with all chronic diseases (hypertension, coronary artery disease, etc.) clinically stable.
- participants must have adequate cognitive function to be able to give informed consent. This will be established by enrolling participants with CLOX 1 scores of ≥10.
Who cannot join
- unstable ischemic heart disease
- clinically significant pulmonary disease
- history of immunodeficiency or receiving immunosuppressive therapy
- history of a coagulopathy or receiving a medical condition requiring anticoagulation
- an estimated glomerular filtration rate of <30ml/min
- uncontrolled hypercholesteremia >350mg/dl;
Show all 12Show fewer
- uncontrolled hypertriglyceridemia >500mg/dl
- diabetes
- history of skin ulcers or poor wound healing
- smoking
- liver disease
- treatment with drugs known to affect cytochrome P450 3A (diltiazem, erythromycin)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Mammalian Target of Rapamycin Inhibition and Other Metabolism Modulating Interventions on the Elderly: Immune, Cognitive, and Functional Consequences
The ability to mount an effective immune response declines with age, leaving the elderly increasingly susceptible to infectious diseases and cancer. Rapamycin, an FDA approved drug to prevent transplant rejection, increases the lifespan and healthspan of mice and ameliorates age-related declines in immune responsiveness, cancer survival, and cognition in laboratory animals. Investigators are conducting a translational trial to test whether rapamycin also improves life functions in humans focusing on elderly persons (aged 70-95).
Read the detailed description
Inhibition of the mTOR pathway by rapamycin (RAPA), an immunosuppressive drug used as adjunct therapy in preventing solid organ allograft rejection, enhances longevity in mice. Importantly, RAPA was efficacious even when initiated in relatively old animals. Thus, it has been suggested that RAPA could be used therapeutically in humans to slow age-associated pathologies. Indeed, improvements in cognition, control of tumorigenesis, and enhancing certain aspects of immunity have been demonstrated in RAPA treated murine models. Moreover, long-term RAPA delivery in older mice is associated with changes in immune reactivity not evident in younger animals. Investigators propose to expand to a larger cohort of older humans to test the hypothesis that RAPA treatment, even in very old individuals, will result in simultaneous improvement in systems known to be negatively affected by aging. Investigators will focus on the immune system, cognition, and physical parameters of healthy aging, such as walking speed. Investigators will recruit healthy volunteers, aged 75-95 years, and randomize them to either RAPA or placebo, controlling for gender, ethnicity, and age. These groups will be used to address the following specific aims: Aim 1. Assess general parameters of immune health before and after RAPA treatment; these include serum inflammatory cytokines, PBMC subsets (naïve vs memory T cells, TREGS, etc.), and polyclonal T cell activation potential. Aim 2. Test the effects of RAPA treatment on responsiveness to a vaccine challenge; both B cell (antibody) and T cell responses will be assessed. Aim 3. Correlate immune function rejuvenation with cognitive and physical function measures in subjects treated with RAPA or placebo. Aim 4. Collect pilot data on effect of RAPA on cardiovascular function. Cognition will be assessed by three different testing tools (EXIT25, SLUMS, and TAPS). Physical performance will be measured by grip strength and 40 foot timed walks, parameters known to correlate with healthy aging. Measures of cardiovascular function (Substudy D) using MRI of the heart to evaluate diastolic function and brain MRI to analyze cerebral blood flow, with measures of pulse wave velocity and endothelial function using laser doppler flowmetry will be performed. In addition to scoring positive outcomes, investigators will assess whether there are adverse changes in clinical laboratory tests that could compromise the safe use of RAPA therapeutically in older individuals. The long-term goal is to assess whether RAPA is safe to use in an elderly population, while also being efficacious in slowing, or even reversing, the aging process.
- Conditions
- Aging
- Being tested
- Rapamycin, Placebo
- Keywords
- Geriatrics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RapamycinDrug
Also called Sirolimus
treatment
PlaceboDrug
control
RapamycinDrug
Also called Sirolimus
No placebo control in this substudy group
| Study group | Role | What they receive |
|---|---|---|
| Rapamycin | Experimental | Rapamycin 1mg taken once daily for 8 weeks Receives: Drug: Rapamycin |
| Placebo | Placebo comparator | Placebo taken once daily for 8 weeks Receives: Drug: Placebo |
| Rapamycin Alone - Cardiovascular Effects | Experimental | No placebo control; Rapamycin 1mg once daily for 8 weeks Receives: Drug: Rapamycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Immunological Responses
T cell function measured by number of T cells per millimeter cubed.
Measured: 8 weeks
Secondary outcomes (2)
Physical Performance
walking speed: Timed 40-foot walk: each participant will perform 3 walks (timed with a stopwatch) at their preferred walking speed over a measured 40-foot path. Results will be averaged for analysis. The faster the walking speed the better the performance.
Measured: 8 weeks
Cognitive Function
The Executive Interview (EXIT25) - This test is a brief bedside test that consists of 25 items measuring abilities that include:
Executive functioning, Motor sequencing, Spoken alternate sequencing, Verbal fluency, Design fluency, Persistence, Resistance to interference, Reflexes Scoring directions are listed under each of the 25 portions of this test. For each section, the client is given a score of a 0, 1, or 2. A score "0" indicates no impairment, a score of "1" indicates some impairment, and a score of "2" indicates severe impairment. Directions for what qualifies as each score are listed under each section. The points are totaled and criteria are given for severe, moderate, and no impairment. Minimum score is -0- and maximum is 50. A score of 15 or below indicates normal executive functioning, a score of above 15 indicates moderate to severe impairment.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2016 (estimated)
- Study startJun 2016
- Primary completionSep 2018
- Study completionSep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for AgingStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center at San AntonioThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dean Kellogg, MD PhD, Principal investigator, University of Texas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02874924
- Sponsor's protocol ID
- HSC20120304H
- Status last verified
- Mar 2018
- First submitted
- 14 Jun 2016
- Last updated
- 4 Dec 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Mammalian Target of Rapamycin Inhibition and Other Metabolism Modulating Interventions on the Elderly: Immune, Cognitive, and Functional Consequences
- ClinicalTrials.gov ID
- NCT02874924
- Acronym / sponsor ID
- HSC20120304H
- Conditions
- Aging
- Keywords
- Geriatrics
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center at San AntonioUniversity, hospital or other
- Study start
- Jun 2016
- Primary completion
- Sep 2018 (actual)
- Study completion
- Sep 2018 (actual)
- First posted
- 22 Aug 2016 (estimated)
- Results
- Posted 4 Dec 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The ability to mount an effective immune response declines with age, leaving the elderly increasingly susceptible to infectious diseases and cancer. Rapamycin, an FDA approved drug to prevent transplant rejection, increases the lifespan and healthspan of mice and ameliorates age-related declines in immune responsiveness, cancer survival, and cognition in laboratory animals. Investigators are conducting a translational trial to test whether rapamycin also improves life functions in humans focusing on elderly persons (aged 70-95).
Detailed description
Inhibition of the mTOR pathway by rapamycin (RAPA), an immunosuppressive drug used as adjunct therapy in preventing solid organ allograft rejection, enhances longevity in mice. Importantly, RAPA was efficacious even when initiated in relatively old animals. Thus, it has been suggested that RAPA could be used therapeutically in humans to slow age-associated pathologies. Indeed, improvements in cognition, control of tumorigenesis, and enhancing certain aspects of immunity have been demonstrated in RAPA treated murine models. Moreover, long-term RAPA delivery in older mice is associated with changes in immune reactivity not evident in younger animals. Investigators propose to expand to a larger cohort of older humans to test the hypothesis that RAPA treatment, even in very old individuals, will result in simultaneous improvement in systems known to be negatively affected by aging. Investigators will focus on the immune system, cognition, and physical parameters of healthy aging, such as walking speed. Investigators will recruit healthy volunteers, aged 75-95 years, and randomize them to either RAPA or placebo, controlling for gender, ethnicity, and age. These groups will be used to address the following specific aims: Aim 1. Assess general parameters of immune health before and after RAPA treatment; these include serum inflammatory cytokines, PBMC subsets (naïve vs memory T cells, TREGS, etc.), and polyclonal T cell activation potential. Aim 2. Test the effects of RAPA treatment on responsiveness to a vaccine challenge; both B cell (antibody) and T cell responses will be assessed. Aim 3. Correlate immune function rejuvenation with cognitive and physical function measures in subjects treated with RAPA or placebo. Aim 4. Collect pilot data on effect of RAPA on cardiovascular function. Cognition will be assessed by three different testing tools (EXIT25, SLUMS, and TAPS). Physical performance will be measured by grip strength and 40 foot timed walks, parameters known to correlate with healthy aging. Measures of cardiovascular function (Substudy D) using MRI of the heart to evaluate diastolic function and brain MRI to analyze cerebral blood flow, with measures of pulse wave velocity and endothelial function using laser doppler flowmetry will be performed. In addition to scoring positive outcomes, investigators will assess whether there are adverse changes in clinical laboratory tests that could compromise the safe use of RAPA therapeutically in older individuals. The long-term goal is to assess whether RAPA is safe to use in an elderly population, while also being efficacious in slowing, or even reversing, the aging process.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Rapamycin | Experimental | Drug: RapamycinRapamycin 1mg taken once daily for 8 weeks |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo taken once daily for 8 weeks |
| Rapamycin Alone - Cardiovascular Effects | Experimental | Drug: RapamycinNo placebo control; Rapamycin 1mg once daily for 8 weeks |
Who may qualify
- Ages
- 70 to 95 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (2 listed)
- participants will be in good health with all chronic diseases (hypertension, coronary artery disease, etc.) clinically stable.
- participants must have adequate cognitive function to be able to give informed consent. This will be established by enrolling participants with CLOX 1 scores of ≥10.
Key exclusion criteria (12 listed)
- unstable ischemic heart disease
- clinically significant pulmonary disease
- history of immunodeficiency or receiving immunosuppressive therapy
- history of a coagulopathy or receiving a medical condition requiring anticoagulation
- an estimated glomerular filtration rate of <30ml/min
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RapamycinAlso: Sirolimustreatment | Drug | Rapamycin |
| Placebocontrol | Drug | Placebo |
| RapamycinAlso: SirolimusNo placebo control in this substudy group | Drug | Rapamycin Alone - Cardiovascular Effects |
Primary outcome
Immunological Responses
Time frame: 8 weeks
T cell function measured by number of T cells per millimeter cubed.
2 secondary outcomes
Physical Performance
Time frame: 8 weeks
Cognitive Function
Time frame: 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dean Kellogg, MD PhD principal investigator
University of Texas
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rapamycin in people with Aging, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Immunological Responses (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2018.