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
Introduction:Geroscience studies of low-dose rapamycin in laboratory species have identified numerous benefits, including reversing age-related cardiac dysfunction. Cardiovascular benefits have been observed in dogs with 10 weeks of treatment, raising questions about possible benefits and adverse ef...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-05-01
|
| Series: | Frontiers in Veterinary Science |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fvets.2023.1168711/full |
| _version_ | 1827944720432627712 |
|---|---|
| author | Brian G. Barnett Sonya R. Wesselowski Sonya G. Gordon Ashley B. Saunders Daniel E. L. Promislow Daniel E. L. Promislow Stephen M. Schwartz Lucy Chou Jeremy B. Evans Matt Kaeberlein Kate E. Creevy |
| author_facet | Brian G. Barnett Sonya R. Wesselowski Sonya G. Gordon Ashley B. Saunders Daniel E. L. Promislow Daniel E. L. Promislow Stephen M. Schwartz Lucy Chou Jeremy B. Evans Matt Kaeberlein Kate E. Creevy |
| author_sort | Brian G. Barnett |
| collection | DOAJ |
| description | Introduction:Geroscience studies of low-dose rapamycin in laboratory species have identified numerous benefits, including reversing age-related cardiac dysfunction. Cardiovascular benefits have been observed in dogs with 10 weeks of treatment, raising questions about possible benefits and adverse effects of long-term use of low-dose rapamycin. 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.Methods: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. Three-month evaluation included physical examination and clinicopathology. Owners completed online questionnaires every 2 weeks.Results: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).Discussion: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. |
| first_indexed | 2024-03-13T10:34:32Z |
| format | Article |
| id | doaj.art-ef31f02892114e298f3e2dcb672c9fd0 |
| institution | Directory Open Access Journal |
| issn | 2297-1769 |
| language | English |
| last_indexed | 2024-03-13T10:34:32Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Veterinary Science |
| spelling | doaj.art-ef31f02892114e298f3e2dcb672c9fd02023-05-18T08:05:19ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692023-05-011010.3389/fvets.2023.11687111168711A masked, placebo-controlled, randomized clinical trial evaluating safety and the effect on cardiac function of low-dose rapamycin in 17 healthy client-owned dogsBrian G. Barnett0Sonya R. Wesselowski1Sonya G. Gordon2Ashley B. Saunders3Daniel E. L. Promislow4Daniel E. L. Promislow5Stephen M. Schwartz6Lucy Chou7Jeremy B. Evans8Matt Kaeberlein9Kate E. Creevy10Department of Small Animal Clinical Sciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, United StatesDepartment of Small Animal Clinical Sciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, United StatesDepartment of Small Animal Clinical Sciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, United StatesDepartment of Small Animal Clinical Sciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, United StatesDepartment of Biology, University of Washington, Seattle, WA, United StatesDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United StatesEpidemiology Program, Fred Hutchinson Cancer Center, Seattle, WA, United StatesDepartment of Small Animal Clinical Sciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, United StatesDepartment of Small Animal Clinical Sciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, United StatesDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United StatesDepartment of Small Animal Clinical Sciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, United StatesIntroduction:Geroscience studies of low-dose rapamycin in laboratory species have identified numerous benefits, including reversing age-related cardiac dysfunction. Cardiovascular benefits have been observed in dogs with 10 weeks of treatment, raising questions about possible benefits and adverse effects of long-term use of low-dose rapamycin. 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.Methods: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. Three-month evaluation included physical examination and clinicopathology. Owners completed online questionnaires every 2 weeks.Results: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).Discussion: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.https://www.frontiersin.org/articles/10.3389/fvets.2023.1168711/fulldiastolic functionagingage-related declineechocardiographygeroscience |
| spellingShingle | Brian G. Barnett Sonya R. Wesselowski Sonya G. Gordon Ashley B. Saunders Daniel E. L. Promislow Daniel E. L. Promislow Stephen M. Schwartz Lucy Chou Jeremy B. Evans Matt Kaeberlein Kate E. Creevy 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 Frontiers in Veterinary Science diastolic function aging age-related decline echocardiography geroscience |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | masked placebo controlled randomized clinical trial evaluating safety and the effect on cardiac function of low dose rapamycin in 17 healthy client owned dogs |
| topic | diastolic function aging age-related decline echocardiography geroscience |
| url | https://www.frontiersin.org/articles/10.3389/fvets.2023.1168711/full |
| work_keys_str_mv | AT briangbarnett amaskedplacebocontrolledrandomizedclinicaltrialevaluatingsafetyandtheeffectoncardiacfunctionoflowdoserapamycinin17healthyclientowneddogs AT sonyarwesselowski amaskedplacebocontrolledrandomizedclinicaltrialevaluatingsafetyandtheeffectoncardiacfunctionoflowdoserapamycinin17healthyclientowneddogs AT sonyaggordon amaskedplacebocontrolledrandomizedclinicaltrialevaluatingsafetyandtheeffectoncardiacfunctionoflowdoserapamycinin17healthyclientowneddogs AT ashleybsaunders amaskedplacebocontrolledrandomizedclinicaltrialevaluatingsafetyandtheeffectoncardiacfunctionoflowdoserapamycinin17healthyclientowneddogs AT danielelpromislow amaskedplacebocontrolledrandomizedclinicaltrialevaluatingsafetyandtheeffectoncardiacfunctionoflowdoserapamycinin17healthyclientowneddogs AT danielelpromislow amaskedplacebocontrolledrandomizedclinicaltrialevaluatingsafetyandtheeffectoncardiacfunctionoflowdoserapamycinin17healthyclientowneddogs AT stephenmschwartz amaskedplacebocontrolledrandomizedclinicaltrialevaluatingsafetyandtheeffectoncardiacfunctionoflowdoserapamycinin17healthyclientowneddogs AT lucychou amaskedplacebocontrolledrandomizedclinicaltrialevaluatingsafetyandtheeffectoncardiacfunctionoflowdoserapamycinin17healthyclientowneddogs AT jeremybevans amaskedplacebocontrolledrandomizedclinicaltrialevaluatingsafetyandtheeffectoncardiacfunctionoflowdoserapamycinin17healthyclientowneddogs AT mattkaeberlein amaskedplacebocontrolledrandomizedclinicaltrialevaluatingsafetyandtheeffectoncardiacfunctionoflowdoserapamycinin17healthyclientowneddogs AT kateecreevy amaskedplacebocontrolledrandomizedclinicaltrialevaluatingsafetyandtheeffectoncardiacfunctionoflowdoserapamycinin17healthyclientowneddogs AT briangbarnett maskedplacebocontrolledrandomizedclinicaltrialevaluatingsafetyandtheeffectoncardiacfunctionoflowdoserapamycinin17healthyclientowneddogs AT sonyarwesselowski maskedplacebocontrolledrandomizedclinicaltrialevaluatingsafetyandtheeffectoncardiacfunctionoflowdoserapamycinin17healthyclientowneddogs AT sonyaggordon maskedplacebocontrolledrandomizedclinicaltrialevaluatingsafetyandtheeffectoncardiacfunctionoflowdoserapamycinin17healthyclientowneddogs AT ashleybsaunders maskedplacebocontrolledrandomizedclinicaltrialevaluatingsafetyandtheeffectoncardiacfunctionoflowdoserapamycinin17healthyclientowneddogs AT danielelpromislow maskedplacebocontrolledrandomizedclinicaltrialevaluatingsafetyandtheeffectoncardiacfunctionoflowdoserapamycinin17healthyclientowneddogs AT danielelpromislow maskedplacebocontrolledrandomizedclinicaltrialevaluatingsafetyandtheeffectoncardiacfunctionoflowdoserapamycinin17healthyclientowneddogs AT stephenmschwartz maskedplacebocontrolledrandomizedclinicaltrialevaluatingsafetyandtheeffectoncardiacfunctionoflowdoserapamycinin17healthyclientowneddogs AT lucychou maskedplacebocontrolledrandomizedclinicaltrialevaluatingsafetyandtheeffectoncardiacfunctionoflowdoserapamycinin17healthyclientowneddogs AT jeremybevans maskedplacebocontrolledrandomizedclinicaltrialevaluatingsafetyandtheeffectoncardiacfunctionoflowdoserapamycinin17healthyclientowneddogs AT mattkaeberlein maskedplacebocontrolledrandomizedclinicaltrialevaluatingsafetyandtheeffectoncardiacfunctionoflowdoserapamycinin17healthyclientowneddogs AT kateecreevy maskedplacebocontrolledrandomizedclinicaltrialevaluatingsafetyandtheeffectoncardiacfunctionoflowdoserapamycinin17healthyclientowneddogs |