Short-term (10-week) rapamycin randomized controlled trial in 24 middle-aged companion dogs
Twenty-four middle-aged healthy pet dogs received placebo or a non-immunosuppressive dose of rapamycin for 10 weeks in a randomized controlled trial whose primary goal was establishing safety, with echocardiography before and after treatment. No clinical side effects were seen in the rapamycin group, and echocardiography suggested improvement in diastolic and systolic age-related measures of heart function (E/A ratio, fractional shortening, ejection fraction). Hematology stayed within normal ranges apart from a decreased mean corpuscular volume in treated dogs. A companion pharmacokinetic study in 5 healthy purpose-bred hounds showed that oral low-dose (0.1 mg/kg) rapamycin achieved blood concentrations measurable in nanograms per milliliter.
Record
| Design | randomized controlled trial |
|---|---|
| Status | completed |
| Setting | client owned |
| Intervention | Rapamycin at a non-immunosuppressive dose |
| Intervention class | drug |
| Comparator | placebo |
| Dose regimen | 0.05 mg/kg three times weekly in one rapamycin treatment group and 0.1 mg/kg three times weekly in another rapamycin treatment group (as described in the 2023 Texas A&M follow-up trial); the 2017 abstract states only a non-immunosuppressive dose for 10 weeks |
| Duration | 10 weeks |
| Dogs | 24 |
| Population note | 24 middle-aged healthy dogs received either placebo or rapamycin |
| Age | Middle-aged; mean age of 9.7 years (as reported in the 2023 follow-up trial) |
| Other | Healthy pet dogs |
| Primary outcome | Safety of low-dose rapamycin (clinical and hematological exams before, during and after the trial) and echocardiographic measures of heart function before and after the trial |
| Result (as reported) | No clinical side effects in the rapamycin-treated group compared to dogs receiving the placebo. Echocardiography suggested improvement in both diastolic and systolic age-related measures of heart function (E/A ratio, fractional shortening, and ejection fraction) in the rapamycin-treated dogs. Hematological values remained within the normal range for all parameters studied; however, the mean corpuscular volume (MCV) was decreased in rapamycin-treated dogs. |
| Tags | rapamycin, cardiac-function, safety, companion-dogs, short-term, pharmacokinetics |
Notes: The 2016 pharmacokinetic paper (5 purpose-bred hounds, 0.1 mg/kg orally, University of Tennessee IACUC) is grouped here as the pharmacokinetic companion per the registry's grouping decision; its abstract frames its purpose around tumor-bearing dogs and does not itself reference the 10-week trial. Dose groups, randomization wording and mean age of the 10-week trial are taken from the 2023 Texas A&M follow-up trial's description of the prior trial; the 2017 abstract itself does not name the dose, the lead institution or the funder. The low-dose rapamycin pharmacokinetic study (PMID 26709938; University of Tennessee, 5 purpose-bred hounds) is a separate study and is not a source of this record.
Sources and verbatim quotes
A randomized controlled trial to establish effects of short-term rapamycin treatment in 24 middle-aged companion dogs. (2017) PMID 28374166 (results)
In this study, 24 middle-aged healthy dogs received either placebo or a non-immunosuppressive dose of rapamycin for 10 weeks.
All dogs received clinical and hematological exams before, during, and after the trial and echocardiography before and after the trial.
Our results showed no clinical side effects in the rapamycin-treated group compared to dogs receiving the placebo.
Echocardiography suggested improvement in both diastolic and systolic age-related measures of heart function (E/A ratio, fractional shortening, and ejection fraction) in the rapamycin-treated dogs.
Hematological values remained within the normal range for all parameters studied; however, the mean corpuscular volume (MCV) was decreased in rapamycin-treated dogs.
Based on these results, we will test rapamycin on a larger dog cohort for a longer period of time in order to validate its effects on cardiac function and to determine whether it can significantly improve healthspan and reduce mortality in companion dogs.
A masked, placebo-controlled, randomized clinical trial evaluating safety and the effect on cardiac function of low-dose rapamycin in 17 healthy client-owned dogs. (2023) PMID 37275618 (follow-up)
Previously, our group investigated low-dose rapamycin and placebo treatments in healthy, middle-aged dogs over a 10-week period, with the primary goal of establishing the safety of low-dose rapamycin in healthy pet dogs.
Interestingly, this trial found that FS improved in treated dogs, although a statistically significant change in EF was not detected, over the 10-week study period.
which showed significantly higher FS and E/A ratio in dogs treated with a shorter duration but higher dose of rapamycin compared to a placebo group in a randomized controlled trial
Dogs in the previous trial received 0.05 mg/kg three times weekly in one rapamycin treatment group and 0.1 mg/kg three times weekly in another rapamycin treatment group (both compared to a placebo group in that trial)
Additionally, dogs in the previous trial had a mean age of 9.7 years
Reproduce: canine_trial_search(trial_id="rapamycin-10-week-rct-2017") in dog-geroscience-mcp; dataset canine-trial-registry.