Clinical trial NCT06745544: Impact of Screening and Multicomponent Exercise on Fall Rates, Fractures, and Cardiovascular Health in Diabetes
Official title: Impact of Screening and Multicomponent Exercise on Fall Rates, Fractures, and Cardiovascular Health in Diabetes: Protocol for a Randomized Control Trial: DIACTIVE
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Type 2 Diabetes
Osteoporosis
Diabetic Neuropathies
Fall Prevention
Cardiovascular Diseases
Keywords: Diabetes
T1D
T2D
RYMA
Falls
Neuropathy
CVD
Diabetic Complications
Bone health
Fractures
Lead sponsor: Aalborg University Hospital
Sponsor class: OTHER
Collaborators: name: Aalborg University
name: Maastricht University Medical Center
First posted: 2024-12-20
Enrollment: 490
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study follows a randomized controlled trial design. Participants are randomly allocated to either the 26 weeks RYMA/ADL exercise intervention group or the control group (usual care). Baseline measures are performed at day 0. Then, follow-up regardless of group is after 26, 52 and 104 weeks and a final visit after 5 years from baseline.
Primary purpose: PREVENTION

Brief summary: The DIACTIVE study is a randomized controlled trial with a 5- year follow-up designed to evaluate the impact of comprehensive screening and multicomponent interventions on fall prevention, bone health, nerve function and cardiovascular outcomes in people with diabetes aged 65 years and older on the short and longer term. Diabetes significantly increases risks of falls, fractures, and cardiovascular disease, yet these areas remain underexplored in clinical research. This trial addresses these gaps with a novel, multidimensional approach.

Participants undergo extensive baseline assessments, including fall risk stratification, bone mineral density measurements via DXA scans, neuropathy evaluations, and cardiovascular profiling. Based on these evaluations, participants are allocated to risk-based intervention arms. The study's centerpiece is the RYMA and ADL exercise program, a tailored cognitive-motor training regimen integrating strength, balance, and executive function exercises with music-based coordination tasks. Pharmacological treatments for osteoporosis and optimization of cardiovascular risk profiles (e.g., SGLT2 inhibitors, GLP-1 agonists) are also incorporated.

Primary outcomes focus on reducing fall rates by at least 30%, improving bone density, mitigating fracture risks, enhancing nerve function, and lowering cardiovascular event rates. Secondary endpoints explore mechanisms underlying fall reduction, quality of life improvements, and adherence to interventions. Advanced methodologies such as gait analysis, seismocardiography, and magnetic resonance imaging (MRI) provide detailed insights into the intervention's effects. Follow-ups at 26 weeks, 52 weeks, 2 years, and 5 years ensure long-term efficacy evaluation.

This trial is conducted at Steno Diabetes Center North and involves interdisciplinary collaboration. By addressing key complications of diabetes through integrated care, the study aims to improve patient outcomes and inform future healthcare strategies for older people with diabetes.

Detailed description: The DIACTIVE study is a randomized controlled trial with a 5-year follow-up designed to assess the effectiveness of a comprehensive intervention targeting fall prevention, bone health, nerve function and cardiovascular outcomes in people with diabetes aged 65 years and older. This innovative research seeks to address critical health vulnerabilities associated with diabetes, particularly the elevated risks of falls, fractures, and cardiovascular diseases (CVD). The study's integrated approach involves advanced screening techniques, tailored interventions, and long-term follow-ups, providing new insights into diabetes management for older populations. Diabetes mellitus (DM) is a chronic condition with rising global prevalence, projected to affect over 783 million people by 2045. While much attention has been given to micro- and macrovascular complications, less focus has been placed on other significant diabetes-related concerns such as bone health, neuropathy, and fall risk. Diabetes exacerbates age-related declines in musculoskeletal strength, sensory function, and cardiovascular resilience, increasing risks of falls and fractures. The interplay between these factors remains underexplored, necessitating multidimensional approaches to care. The DIACTIVE trial addresses these gaps by integrating advanced fall screening, comprehensive bone health evaluations, and cardiovascular profiling with targeted interventions. Its cornerstone is the RYMA exercise program, a novel, music-based training regimen that combines physical and cognitive elements to enhance balance, strength, and executive function.

The study has several primary objectives: reducing fall rates by 30% after 26 weeks of intervention, sustained at 52 weeks and beyond; improving bone mineral density (BMD) and mitigating fracture risks; lowering cardiovascular event rates and improving key cardiovascular markers; enhancing nerve function and reducing the progression of diabetic peripheral neuropathy (DPN); and improving psychological and social outcomes, including reduced fear of falling, enhanced mobility, and better mental well-being. This trial adopts a prospective, randomized controlled design and includes recruitment and screening of people aged ≥65 years with T1D or T2D from outpatient diabetes clinics. Participants undergo comprehensive baseline assessments, including DXA scans for BMD, fall risk stratification, neuropathy evaluations, and cardiovascular profiling using blood pressure, ECG, and advanced imaging techniques like MRI and seismocardiography. Based on their risk profiles, participants are randomized into intervention and control groups. The intervention group engages in the RYMA exercise program, which combines physical and cognitive training elements, including multitasking, reaction-based exercises, and coordination tasks, set to improvised piano music. Pharmacological treatments for osteoporosis and cardiovascular optimization are implemented as per ADA and local guidelines. Outcomes are assessed at 26 weeks, 52 weeks, 2 years, and 5 years, covering fall rates, BMD, nerve function, cardiovascular health, and quality of life.

The RYMA exercise program is the core intervention and focuses on cognitive-motor training through rhythm-based exercises. It targets key risk factors for falls by improving balance, strength, executive function, and coordination while integrating social elements to enhance adherence and sustainability. Bone health interventions involve stratification based on DXA results, with pharmacological treatments for osteoporosis provided according to ADA guidelines. Cardiovascular optimization includes medications such as SGLT2 inhibitors, GLP-1 receptor agonists, and statins, tailored to the participants' risk profiles. The study's primary endpoints include reducing fall rates, improving BMD, reducing fracture risk, optimizing cardiovascular outcomes, and enhancing nerve function. Secondary endpoints focus on understanding the mechanisms underlying these improvements, quality-of-life metrics, and participant adherence to the interventions.

Assessments include validated fall risk algorithms, DXA scans, neuropathy tests (e.g., NC-Stat DPNCheck, vibration perception thresholds, and sensory testing), cardiovascular imaging (e.g., MRI, seismocardiography), and cognitive and physical performance evaluations. Gait analysis, postural stability, muscle strength, and executive function tests provide insights into the intervention's mechanistic effects. The trial aims to recruit 440 participants (220 T1D and 220 T2D). Inclusion criteria are: age ≥65 years, confirmed diagnosis of diabetes for at least one year, and the ability to live independently and participate in the exercise program. Exclusion criteria include severe cognitive impairment, neurological or orthopedic conditions affecting mobility, and participation in other interventional studies within six months.

This study represents a paradigm shift in diabetes management by addressing interconnected health risks through a holistic approach. Its multidisciplinary interventions combine physical, cognitive, and pharmacological elements to improve outcomes in older people with diabetes. By targeting fall prevention, bone health, and cardiovascular risk factors simultaneously, DIACTIVE has the potential to significantly enhance the quality of life and inform future healthcare strategies. Findings from the study will contribute to clinical guidelines, emphasizing integrated care models and tailored interventions for high-risk populations. Long-term follow-ups will provide critical data on the sustainability and scalability of such programs, paving the way for broader implementation in healthcare systems

Eligibility criteria: Inclusion Criteria:

1. Men and women with either T1D or T2D with a minimum of 65 years of age with no upper limit.
2. Living in their own home
3. A diagnosis of diabetes at least one year prior to inclusion of the study to avoid honeymoon diabetes.
4. Signed the informed consent.

Exclusion Criteria:

1. No previous experience with rhythm-based multitask exercise.
2. Having significant neurological diseases (e.g., Parkinson's and Multiple Sclerosis), vestibular diseases, or orthopedic surgeries (e.g., hip/knee replacement) affecting their ability to participate in the study.
3. Having severely impaired cognitive function, defined as a score below 8 on the cognitive assessment "the short orientation-memory-concentration test."
4. Being fully dependent on walking aids.
5. Pregnancy or breast feeding
6. Active malignancy or terminally ill.
7. Not being able to understand Danish written and/or verbally.
8. Participating in other interventional clinical studies within the last six months
9. People with a weekly exercise activity above 5 hours a week

Primary outcomes:
measure: Reduction in Fall Rates
timeFrame: Measurements will take place at 26 weeks, 52 weeks, 104 weeks, and 5 years post-intervention to evaluate both short- and long-term effects of the intervention.
measure: Improvement in Bone Mineral Density (BMD)
timeFrame: Measurements will assess changes at 26 weeks, 52 weeks, 104 weeks, and 5 years post-intervention to evaluate sustained benefits.
measure: Reduction in Cardiovascular Risk and Events
timeFrame: 26 weeks, 52 weeks, 104 weeks, and 5 years post-intervention.
measure: Improvement in Nerve Function
timeFrame: 26 weeks, 52 weeks, 104 weeks, and 5 years post-intervention.
measure: Blood glucose changes
timeFrame: HbA1c measurements will take place at baseline and after 26 weeks, 52 weeks, 104 weeks, and 5 years post-intervention to evaluate both short- and long-term effects of the intervention. CGM will be measures blinded during the 26 weeks RYMA intervention.
Secondary outcomes:
measure: Mechanisms associated with Fall Reduction
timeFrame: 26 weeks, 52 weeks, 104 weeks, and 5 years post-intervention
measure: Improvement in Quality of Life
timeFrame: 26 weeks, 52 weeks, 104 weeks, and 5 years post-intervention
measure: Reduction in Fracture Risk
timeFrame: 52 weeks, 104 weeks, and 5 years post-intervention.
measure: Improvement in Cardiovascular Function
timeFrame: 26 weeks, 52 weeks, 104 weeks, and 5 years post-intervention.
measure: Improvement in Cognitive Function
timeFrame: 26 weeks, 52 weeks, 104 weeks, and 5 years post-intervention.
measure: Membran properties
timeFrame: year 2 and year 5
Other outcomes:
measure: Sustainability of Intervention Effects
timeFrame: 2 years and 5 years post-intervention.
measure: Changes in Muscle Mass and Composition
timeFrame: 26 weeks, 52 weeks, 104 weeks, and 5 years post-intervention.
measure: Changes in Inflammatory Biomarkers
timeFrame: 26 weeks, 52 weeks, and 104 weeks post-intervention.
Locations:
city: Aalborg
country: Denmark
facility: Steno Diabetes Center North
state: Norh
Study officials:
References:
citation: Rolke R, Magerl W, Campbell KA, Schalber C, Caspari S, Birklein F, Treede RD. Quantitative sensory testing: a comprehensive protocol for clinical trials. Eur J Pain. 2006 Jan;10(1):77-88. doi: 10.1016/j.ejpain.2005.02.003.
citation: Mahalingasivam AA, Jespersen AK, Ejskjaer N, Hougaard DD, Vestergaard P, Rasmussen NH, Roikjer J. The co-existence of peripheral and vestibular neuropathy in diabetes: a cross-sectional study. Eur Arch Otorhinolaryngol. 2024 Feb;281(2):663-672. doi: 10.1007/s00405-023-08130-6. Epub 2023 Jul 29.
citation: Jansen S, Bhangu J, de Rooij S, Daams J, Kenny RA, van der Velde N. The Association of Cardiovascular Disorders and Falls: A Systematic Review. J Am Med Dir Assoc. 2016 Mar 1;17(3):193-9. doi: 10.1016/j.jamda.2015.08.022. Epub 2015 Oct 9.
citation: Rajbhandari J, Fernandez CJ, Agarwal M, Yeap BXY, Pappachan JM. Diabetic heart disease: A clinical update. World J Diabetes. 2021 Apr 15;12(4):383-406. doi: 10.4239/wjd.v12.i4.383.
citation: Kressig RW, Allali G, Beauchet O. Long-term practice of Jaques-Dalcroze eurhythmics prevents age-related increase of gait variability under a dual task. J Am Geriatr Soc. 2005 Apr;53(4):728-9. doi: 10.1111/j.1532-5415.2005.53228_2.x. No abstract available.
citation: Lord SR, Close JCT. New horizons in falls prevention. Age Ageing. 2018 Jul 1;47(4):492-498. doi: 10.1093/ageing/afy059.
citation: Wollesen B, Wildbredt A, van Schooten KS, Lim ML, Delbaere K. The effects of cognitive-motor training interventions on executive functions in older people: a systematic review and meta-analysis. Eur Rev Aging Phys Act. 2020 Jul 2;17:9. doi: 10.1186/s11556-020-00240-y. eCollection 2020.
citation: Sherrington C, Fairhall N, Kwok W, Wallbank G, Tiedemann A, Michaleff ZA, Ng CACM, Bauman A. Evidence on physical activity and falls prevention for people aged 65+ years: systematic review to inform the WHO guidelines on physical activity and sedentary behaviour. Int J Behav Nutr Phys Act. 2020 Nov 26;17(1):144. doi: 10.1186/s12966-020-01041-3.
citation: Rasmussen NH, Dal J, den Bergh JV, de Vries F, Jensen MH, Vestergaard P. Increased Risk of Falls, Fall-related Injuries and Fractures in People with Type 1 and Type 2 Diabetes - A Nationwide Cohort Study. Curr Drug Saf. 2021;16(1):52-61. doi: 10.2174/1574886315666200908110058.
citation: Langdahl BL, Hofbauer LC, Forfar JC. Cardiovascular Safety and Sclerostin Inhibition. J Clin Endocrinol Metab. 2021 Jun 16;106(7):1845-1853. doi: 10.1210/clinem/dgab193.
citation: Rasmussen NH, Dal J. Falls and Fractures in Diabetes-More than Bone Fragility. Curr Osteoporos Rep. 2019 Jun;17(3):147-156. doi: 10.1007/s11914-019-00513-1.