LY-D6/2 senolytic and NAD+ precursor combination in senior companion dogs with mild to moderate cognitive impairment
A blinded, three-arm randomized controlled trial at North Carolina State University enrolled 70 companion dogs aged 10 years or older with mild to moderate cognitive impairment and allocated them to placebo, low-dose or full-dose LY-D6/2, a proprietary senolytic plus NAD+ precursor combination given as a daily NAD+ precursor and a monthly two-day senolytic course, for 6 months. Primary outcomes were owner-rated CCDR score and activity-monitor data at 3 months. CCDR change differed significantly across groups (p = 0.02) with the largest improvement on the full dose, while activity, in-house cognitive tests, frailty and owner-reported happiness did not differ significantly; the trial was funded by Animal Bioscience.
Record
| Design | randomized controlled trial |
|---|---|
| Status | completed |
| Setting | client owned |
| Intervention | LY-D6/2, a proprietary combination of a senolytic (LY-D6) and an NAD+ precursor (LY-D2), given at low or full dose |
| Intervention class | diet or supplement |
| Comparator | Placebo |
| Dose regimen | NAD+ precursor (or placebo) capsule(s) once daily and the senolytic (or placebo) capsule(s) on two consecutive days each month; low or full dose (amounts not disclosed) |
| Duration | 6 months (3-month primary endpoint, 6-month secondary endpoint) |
| Dogs | 70 |
| Population note | 70 enrolled and allocated to placebo, low or full dose; 59 completed the 3-month primary endpoint and 51 the 6-month secondary endpoint; randomized in blocks of 9 (3 per group) |
| Age | 10 years or older |
| Other | companion dogs with mild to moderate cognitive impairment (CADES), weighing more than 6 kg, able to walk independently; recruited from the local community at NC State |
| Primary outcome | Change in owner-reported Canine Cognitive Dysfunction Rating (CCDR) scale score and change in activity measured with collar-mounted physical activity monitors at 3 months |
| Result (as reported) | There was a significant difference in CCDR score across treatment groups from baseline to the primary endpoint (p = 0.02) with the largest decrease in the full dose group. No difference was detected between groups using in house cognitive testing, and no significant differences between groups in changes in measured activity. The proportion of dogs that improved in frailty and owner-reported activity and happiness was higher in the full dose group but not significantly; adverse events occurred equally across groups. The authors conclude that LY-D6/2 improves owner-assessed cognitive function over a 3-month period. |
| Lead organisation | North Carolina State University College of Veterinary Medicine |
| Sponsor or funder | Animal Bioscience, Boston MA |
| Start year | 2022 |
| Tags | senolytic, nad, supplement, cognition, frailty, activity, client-owned |
Notes: Dose amounts are proprietary and not disclosed. Recruitment ran January 2022 through June 2023; no trial registration is mentioned in the full text.
Sources and verbatim quotes
A randomized, controlled clinical trial demonstrates improved owner-assessed cognitive function in senior dogs receiving a senolytic and NAD+ precursor combination. (2024) PMID 38811634 (results)
Age-related decline in mobility and cognition are associated with cellular senescence and NAD + depletion in dogs and people.
A combination of a novel NAD + precursor and senolytic, LY-D6/2, was examined in this randomized controlled trial.
Seventy dogs with mild to moderate cognitive impairment were enrolled and allocated into placebo, low or full dose groups.
Primary outcomes were change in cognitive impairment measured with the owner-reported Canine Cognitive Dysfunction Rating (CCDR) scale and change in activity measured with physical activity monitors.
Fifty-nine dogs completed evaluations at the 3-month primary endpoint, and 51 reached the 6-month secondary endpoint.
There was a significant difference in CCDR score across treatment groups from baseline to the primary endpoint (p = 0.02) with the largest decrease in the full dose group.
No difference was detected between groups using in house cognitive testing. There were no significant differences between groups in changes in measured activity.
The proportion of dogs that improved in frailty and owner-reported activity levels and happiness was higher in the full dose group than other groups, however this difference was not significant. Adverse events occurred equally across groups.
We conclude that LY-D6/2 improves owner-assessed cognitive function over a 3-month period and may have broader, but more subtle effects on frailty, activity and happiness as reported by owners.
A randomized, controlled clinical trial demonstrates improved owner-assessed cognitive function in senior dogs receiving a senolytic and NAD+ precursor combination. (2024) PMID 38811634 (design)
Companion dogs aged 10 years or older were randomized to receive either placebo or LY-D6/2 combination at two different doses (low and full) with primary outcomes of change in owner assessed cognition and collar mounted physical activity monitor (PAM) assessed activity levels after 3 months.
This blinded, randomized, controlled (RCT) clinical trial was conducted and reported according to the CONSORT and ARRIVE Guidelines with the approval of the North Carolina State University Institutional Animal Care and Use Committee under protocol # 21-376-O.
This 3-arm RCT was designed to evaluate the effect of LY-D6/2 on cognitive function and activity in aged dogs over a 6-month period. The primary endpoint of the study was 3 months and the secondary endpoint was 6 months.
Dogs were randomized in blocks of 9 (3 per group) by the NC State pharmacy using a random number generator. Investigators and owners were blinded to treatment identity until data analysis was complete.
In order to participate, dogs had to be greater than or equal to 10 years of age (senior status), weigh more than 6 kg (dictated by available capsule size), and be able to walk independently with sufficient hearing and vision to be able to perform cognitive tests.
The investigational veterinary product (IVP), LY-D6/2 was a proprietary combination of a senolytic and an NAD+ precursor.
Owners were instructed to administer the NAD+ precursor (or placebo) capsule(s) once daily and the senolytic (or placebo) capsule(s) on two consecutive days each month.
Dogs were recruited from the local community through postings on the NC State CVM clinical trials website and social media from January 2022 through June 2023.
This clinical trial was funded by Animal Bioscience, Boston MA. Animal Bioscience played no role in data acquisition, analysis or presentation.
Reproduce: canine_trial_search(trial_id="ly-d6-2-senolytic-nad-precursor-senior-dogs-rct-2024") in dog-geroscience-mcp; dataset canine-trial-registry.