Six-month low-dose rapamycin masked placebo-controlled randomized trial in 17 healthy client-owned dogs (Texas A&M)
Seventeen healthy client-owned dogs aged 6-10 years and weighing 18-36 kg were randomized at the Texas A&M veterinary teaching hospital to low-dose rapamycin (0.025 mg/kg three times per week) or identical placebo capsules for 6 months, with echocardiography and clinical pathology at baseline, 6 and 12 months. There were no statistically significant differences in echocardiographic parameters between groups at 6 or 12 months and no clinically significant adverse events. Owners of rapamycin-treated dogs reported perceived positive changes in behavior or health in 26.8% of bi-weekly surveys versus 8.1% for placebo (p = 0.04). Enrollment stopped early at 17 of a planned 50 dogs.
Record
| Design | randomized controlled trial |
|---|---|
| Status | completed |
| Setting | client owned |
| Intervention | Low-dose rapamycin |
| Intervention class | drug |
| Comparator | Placebo (lactose capsules identical in appearance) |
| Dose regimen | 0.025 mg/kg rapamycin per dose, orally in capsules, three times per week (Monday, Wednesday and Friday mornings), rounded to the nearest 0.25 mg capsule |
| Duration | 6 months of treatment; evaluations at baseline, 3, 6 and 12 months (final examination 6 months after discontinuation) |
| Dogs | 17 |
| Population note | 17 dogs enrolled and randomized: 9 rapamycin, 8 placebo; the initial design sought 50 dogs but enrollment ceased early |
| Age | 6-10 years (mean 7.8 years in the rapamycin group and 8.5 years in the placebo group) |
| Other | Weighing 18-36 kg, without significant systemic disease; all enrolled dogs resided in Texas; diverse breeds |
| Primary outcome | Echocardiographic indices of diastolic and systolic cardiac function at 6 and 12 months, and occurrence of adverse events; impact on routine clinical pathology was a secondary objective |
| Result (as reported) | There were no statistically significant differences in echocardiographic parameters between rapamycin and placebo groups at 6 or 12 months. No clinically significant adverse events occurred. In 26.8% of the bi-weekly surveys owners whose dogs received rapamycin reported perceived positive changes in behavior or health, compared to 8.1% in the placebo group (p = 0.04). The drug was well-tolerated with no significant adverse events. |
| Lead organisation | Texas A&M University (TAMU) Veterinary Medical Teaching Hospital (VMTH) |
| Sponsor or funder | William H. Donner Foundation; additional support for some authors from the Dog Aging Project (NIA U19 AG057377) |
| Tags | rapamycin, cardiac-function, safety, client-owned, placebo-controlled, texas-a-m |
Notes: The IACUC and Clinical Research Review Committee protocol number 2017–0125 is an ethics approval, not a trial registry entry. Enrollment ceased early (17 of a planned 50 dogs) because of recruitment difficulty and the launch of the multi-center TRIAD trial. This paper is also cited as a follow-up source in rapamycin-10-week-rct-2017 and as a design source in triad-rapamycin.
Sources and verbatim quotes
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 (results)
The objectives of this study were to assess the impact of 6 months of low-dose rapamycin on echocardiographic indices of cardiac function in healthy dogs and to document the occurrence of adverse events.
Seventeen client-owned dogs aged 6-10 years, weighing 18-36 kg, and without significant systemic disease were included in a prospective, randomized, placebo-controlled, masked clinical trial.
Low-dose rapamycin (0.025 mg/kg) or placebo was administered three times per week for 6 months.
Baseline, 6-month, and 12-month evaluation included physical examination, cardiology examination, and clinicopathology.
There were no statistically significant differences in echocardiographic parameters between rapamycin and placebo groups at 6 or 12 months. No clinically significant adverse events occurred.
In 26.8% of the bi-weekly surveys owners whose dogs received rapamycin reported perceived positive changes in behavior or health, compared to 8.1% in the placebo group
While no clinically significant change in cardiac function was observed in dogs treated with low-dose rapamycin, the drug was well-tolerated with no significant adverse events.
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 (design)
This study was a prospective, randomized, placebo-controlled double-masked trial conducted at the Texas A&M University (TAMU) Veterinary Medical Teaching Hospital (VMTH).
Placebo (lactose; PCCA, Houston, TX) capsules were created to be identical in appearance. Dogs in the treatment group were given 0.025 mg/kg rapamycin per dose, rounded to the nearest 0.25 mg capsule. Owners were instructed to give the study medication on Monday, Wednesday, and Friday mornings.
Administration of rapamycin and placebo was continued for a period of 6 months.
A final examination was performed at 12 months (6 months after discontinuation of study medication) to determine whether any changes induced by rapamycin therapy persisted beyond the treatment period.
17 dogs were enrolled and randomly assigned to rapamycin or placebo groups.
six out of nine rapamycin-treated dogs, and five out of eight placebo-treated dogs
the mean age in the present trial was 7.8 years for the treatment group and 8.5 years for the placebo group
Because all enrolled dogs resided in Texas
The diversity of the breeds enrolled may have been a contributing factor as well.
Assessment of the impact of low-dose rapamycin on routine clinical pathology was a secondary objective.
This frequency of positive owner-reported outcomes in the rapamycin treatment group was significantly greater than in the placebo group (*p* = 0.04).
The initial study design sought to enroll 50 dogs (25 placebo, 25 rapamycin) based on power calculations. Several factors caused us to cease enrollment early, limiting the power to detect significant changes in the primary endpoint. These factors included difficulty identifying eligible dogs near the clinical site and the launch of the larger, multi-center clinical trial described below.
This study was funded by the William H. Donner Foundation. Additional support for some authors was provided by the Dog Aging Project (NIA U19 AG057377; BB, DP, MK, JE, LC, and KC).
Institutional Animal Care and Use Committee (IACUC) and Clinical Research Review Committee protocol number 2017–0125.
Reproduce: canine_trial_search(trial_id="rapamycin-6-month-rct-tamu-2023") in dog-geroscience-mcp; dataset canine-trial-registry.