Light Intensity Physical Activity Trial

Not Applicable

Completed

• Conditions: Light Intensity Physical Activity; Aortic Stiffness; Pulse Wave Velocity; Diabetes Mellitus; Type2 Diabetes; Artery Disease; Physical Activity; Physical Exercise; Arterial Stiffness; Sedentary Lifestyle
• Interventions: Behavioral: Workshops control group LiPAT; Behavioral: Interactive workshops LiPAT intervention group; Device: Wrist-worn feedback physical activity monitor; Device: Smartphone application LiPAT; Behavioral: Telephone Coaching

• Registration Number: NCT03415880
• Lead Sponsor: Academisch Ziekenhuis Maastricht

Brief Summary

In type 2 diabetes (T2D), physical activity is an important modifiable risk factor of cardiovascular disease (CVD). Unfortunately (long-term) compliance to exercise programs in patients with T2D is poor. Light-intensity physical activity (LiPA) such as walking slowly, household activities or taking a flight of stairs might be a potential target for lowering the CVD risk in patients with T2D since it can perhaps be more be incorporated into daily life. To assess cardiovascular disease risk in this single-blinded RCT, the investigators settled on measuring arterial stiffness as the primary outcome. Arterial stiffness has independent predictive value for cardiovascular events and can be measured reliably and non-invasively. The investigators hypothesize that light intensity physical activity intervention program based upon increasing LiPA by replacing sedentary time is effective in lowering arterial stiffness as estimated by aortic pulse wave velocity (PWV) and carotid distensibility in individuals with T2D.

Detailed Description

Total duration of the RCT is 12 months, with the first 6 month as the intervention period and the last 6 months as follow-up.

Community-dwelling individuals with type 2 diabetes are eligible for participation in the trial, taking into account the in- and exclusion criteria described below, 160 participants will be included, 80 in each study arm. Study measurements of all participants will take place at baseline (month 1 (t = 0)), month 3 (t = 3), month 6 (t = 6, and month 12 (t = 12) at the Maastricht UMC+.

Participants in the intervention group will be instructed to increase their LiPA by decreasing sedentary time. Participants will follow 4 workshops in group sessions on strategies to change their physical activity behaviour and will receive a feedback physical activity monitor that will be worn continuously on the wrist and provide e-feedback on activity behaviour.

Participants in the control group will receive 4 workshops in group sessions on healthy lifestyle including information and strategies to increase LiPA and reduce sedentary time similar to the intervention group, but will not receive a feedback-activity monitor.

Screening A preliminary screening will be carried out by telephone interview. If eligibility criteria are met the participant will attend the baseline visit which starts with the informed consent procedure. Afterwards, a standard physical examination will take place and an ultrasound scan will be performed to screen for large atherosclerotic plaques of the carotid arteries. If the participant is indeed eligible for inclusion, the investigational baseline measurements are performed after which randomization will take place. From then on participants will run through the protocol either being part of the intervention or control group.

Measurements at the four investigational visits (t = 0, 3, 6 and 12)

* sociodemographic data

* medical history \& medication use: by means of an interview

* lifestyle factors (alcohol use and smoking behaviour), quality of life, depressive symptoms - by means of questionnaires

* Sedentary and physical activity monitoring: by means of the activPAL® activity monitor for 7 days

* venous sampling (approx. 40 ml per person per visit; 8 collecting tubes of 5 ml) for fasting glucose, fasting insulin, HbA1c, lipid profile, creatinin, albumin and biomarkers of endothelial dysfunction (vWF, s-VCAM-1, sE-selectin, sTM, SICAM-1), low-grade inflammation(CRP, SAA, IL-6, TNF-alfa, IL-8) and immune cells. The remainder of the material will be stored in a biobank for future determination of any potentially interesting (bio)markers on the topic of physical activity. For any such future procedures further approval will be sought from the METC/MUMC+.

* Anthropometric data (height, weight, waist and hip circumference and bio-electrical impedance measurements)

* vascular measurement (arterial stiffness, microvascular function and blood pressure)

* physical function measurements (grip strength and timed chair test)

* Objective measurement of light-intensity physical activity through activPAL ® activity monitor that will be worn for 7 days continuously at baseline, month 3, month 6, and month 12. This device is blinded to the participant. Data from the activPAL provide detailed and accurate information on the participants' sedentary, standing, and stepping time for each day.

Sample size calculation In order to be able to detect a 10% difference in PWV and similarly a 10% difference in carotid distensibility (the primary objectives of the study) after the intervention between the intervention group and the control group, both groups should consist of at least 73 participants each if assuming a probability of a type 1 error at 0.05 (i.e., alfa) and an 80% (i.e., beta) ability to detect a true difference between the intervention group and the control group. These estimates are conservative taking into account only PWV values at entry and exit of the trial. The 10% difference is speculative and based upon a mean PWV estimates from 'The Maastricht Study' data as there is currently no data available on LiPA and arterial stiffness. In order to correct for potential drop out (roughly estimated at 10%) 80 participants will be included in each group.

Statistical analysis The significance levels used in the statistical analyses will be 0.05. The validity of the normality assumption will be check for all outcomes. Baseline characteristics will be compared between the intervention and the control group. For continuous variables (e.g. age, BMI) mean and standard deviations will be presented; numbers and percentages will be shown for categorical variables (e.g. smoking, medication use). T-tests will be used to compare differences in continuous baseline characteristics between the intervention and control group and chi-square test will be used for categorical variables. Assuming that the randomization was successful no differences are expected. Missing data will be imputed using multiple imputations techniques.

Primary study parameter(s) The effect of the intervention on the primary outcome PWV at month 6 will be analysed using intention-to-treat (ITT) approach according to randomization assignment. The ITT analyses will be used as primary method for our statistical analyses and any outcomes in our reports will be primarily based upon these ITT analyses. In addition, a per protocol analysis will be performed for those who attended the workshops. These analyses will be used to gain some insights into any potential non-response / drop out. These per protocol analyses will not be the primary source for reporting outcomes. General linear models will be used to analyse the effect of the intervention on PWV at month 6. Due to the COVID-19 crisis some month 6 measurement will take place at a later moment, depending on the duration of this delay we will have to adjust for this in our statistiscal anlayes. In addition, repeated measures will be taken into account, baseline, month 3, and month 6 using mixed models in SPSS. The 3-month visits might be missing for some particiapants due to COVID-19 crisis, we assume that the 6-month measurements for these particiaptns can take place as planned In these models, subject is entered as a random effect and intervention (categorical variable with 2 levels: 1: intervention; 2: control group) as a fixed effect .The baseline value of PVW and sex will be used as covariates in analyses.

Secondary study parameter(s) Sedentary time, as measured by the activPAL will be analysed as total sedentary minutes on an average day as well as the percentage of sedentary during wake time. Similarly, time standing and stepping, also derived from the activPAL data will be analysed. All metabolic health parameters and microcirculation measurements will also be analysed as continuous variables. Quality of life and mental functioning are also analysed as continuous variables. Finally, measures of body composition measures are also all continuous outcomes variables

Similar to the primary outcome analyses, general linear mixed models will be used the analyses the change the secondary outcome measures from baseline to month 6. Using mixed models, the repeated measures will be taken into account similar the analyses with the primary outcome.

All analyses, for the both primary and secondary outcomes will also be conducted for the follow-up (month 12 data) to examine the long-term effect of the intervention, taking into account all repeated measures (baseline, month 3, month 6) in a mixed model.

Study Timeline

• Study First Submitted: 2018-01-08
• Study First Submitted QC: 2018-01-23
• Study First Posted: 2018-01-30
• Study Start: 2018-11-08
• Primary Completion: 2021-12-31
• Study Completion: 2022-02-15
• Status Verified: 2023-01
• Last Update Submitted: 2023-01-31
• Last Update Posted: 2023-02-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 132

Inclusion Criteria

• 40-70 years old
• having type 2 diabetes
• BMI 20-35 kg/m2
• having a sedentary lifestyle (i.e., self-reported moderate-to-vigorous physical activity < 150 minutes per week)
• willingness to undergo randomization
• being in the possession of personally owned smart phone

Exclusion Criteria

• not being able to walk for 15 minutes for any (medical) reason
• currently engaged in an (medical) exercise program
• plan to move out of the study area in the next 12 months
• (digital) illiteracy or being unable to read Dutch
• a history of any cardiovascular event (including stroke) three months prior to possible inclusion
• a history of signs or symptoms of ischemic heart disease and(or) heart failure three months prior to possible inclusion
• a history or signs or symptoms of peripheral arterial disease three months prior to possible inclusion
• a history or signs or symptoms of severe diabetic neuropathy or diabetic foot ulcers three months prior to possible inclusion
• a history of sign or symptoms of severe diabetic retinopathy three months prior to possible inclusion
• a history or sign or symptoms of severe osteoarthritis or severe joint complaints three months prior to possible inclusion
• a history or signs or symptoms of COPD (eligible are those participants with a COPD Gold classification ≤ I)
• uncontrolled diabetes (i.e., uncontrolled hypo- or hyperglycaemia)
• uncontrolled hypertension (i.e., systolic / diastolic blood pressure ≥ 180 / 95 mmHg)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control group	Workshops control group LiPAT	Participants attend 4 workshops and undergo all measurements at t=0, t=3, t=6, and t=12 months.
Intervention group	Smartphone application LiPAT	Participants attend 4 workshops, receive a wrist-worn feedback physical activity monitor, a smartphone app, and telephone coaching. All participants undergo all measurements at t=0, t=3, t=6, and t=12 months.
Intervention group	Wrist-worn feedback physical activity monitor	Participants attend 4 workshops, receive a wrist-worn feedback physical activity monitor, a smartphone app, and telephone coaching. All participants undergo all measurements at t=0, t=3, t=6, and t=12 months.
Intervention group	Telephone Coaching	Participants attend 4 workshops, receive a wrist-worn feedback physical activity monitor, a smartphone app, and telephone coaching. All participants undergo all measurements at t=0, t=3, t=6, and t=12 months.
Intervention group	Interactive workshops LiPAT intervention group	Participants attend 4 workshops, receive a wrist-worn feedback physical activity monitor, a smartphone app, and telephone coaching. All participants undergo all measurements at t=0, t=3, t=6, and t=12 months.

Primary Outcome Measures

Name	Time	Method
The effect of a LiPA intervention program on increasing carotid distensibility in patients with type 2 diabetes.	Change from baseline carotid distensibility at 6 months.	Carotid distensibility will be determined at the left common carotid by means of arterial ultrasound.
The effect of a LiPA intervention program on reducing aortic carotid-to-femoral pulse-wave velocity (PWV) in patients with type 2 diabetes.	Change from baseline PWV at 6 months.	Aortic (carotid to femoral) PWV will be determined by means of applanation tonometry. It will be calculated as the median of three consecutive PWV recordings.

Secondary Outcome Measures

Name	Time	Method
Feasibility of a LiPA intervention program on reducing sedentary time as measured by activPAL	Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).	Daily activity levels will be measured by activPAL3™ physical activity monitor. The participants will wear the device fixated on their upper leg for 8 consecutive days at each measurement moment. ActivPAL measures total standing time, sedentary time (sitting or lying down), and stepping time (physical activity).
The effect of a LiPA intervention on depressive symptoms with the use a validated Dutch version of the 9-item Patient Health Questionnaire (PHQ-9).	Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).	The PHQ-9 is a self-administered questionnaire based on the DMS-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria for a major depressive disorder. It comprises nine items rated on a 4-point scale, ranging from 0 = "not at all" to 3 = "nearly every day". The PHQ-9 scale will also be used as a dichotomous variable with a pre-defined cut-off level of 10, which represents the presence of clinically relevant depressive symptoms.
The effect of a LiPA intervention on triglycerides.	Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).	Measurement of any changes in triglycerides
The effect of a LiPA intervention on changes in blood pressure.	Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).	Measurement of any changes in blood pressure
The effect of a LiPA intervention on body composition	Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).	Measurement of any changes in body composition as measured by bio electrical impedance.
The effect of a LiPA intervention on waist -circumference in cm.	Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).	Measurement of any changes in waist -circumference
The effect of a LiPA intervention on quality of life as measured through the Dutch versions of the EQ-5D questionnaire.	Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).	The EQ-5D is a short questionnaire that covers five dimensions of health: Mobility, Self-Care, Usual Activities, Pain/Discomfort and Anxiety/Depression. The EQ-5D includes 5 questions with 5 answer options each, ranging from 1 ('no problems') to 5 ('severe limitation'). A summary index with a maximum score of 1 can be computed from these five dimensions by means of a converion table. A score of 1 indicates the best health status. Additionally, there is a visual analogue scale (VAS) to indicate the general health status with scores ranging from 0 ('the worst health you can imagine') to 100 ('the best health you can imagine').
The effect of a LiPA intervention program on microvascular function	Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).	Microvascular function will be evaluated in both the retina and the skin. Which will be determined with the use of fundoscopy and Skin laser Doppler flowmetry.
Feasibility of a LiPA intervention program on increasing standing and stepping time as measured by activPAL.	Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).	Daily activity levels will be measured by activPAL3™ physical activity monitor. The participants will wear the device fixated on their upper leg for 8 consecutive days at each measurement moment. ActivPAL measures total standing time, sedentary time (sitting or lying down), and stepping time (physical activity). Stepping time (physical activity) is further classified into higher intensity physical activity (minutes with a step frequency \>110 steps/min during waking time) and lower intensity physical activity (minutes with a step frequency ≤110 steps/min during waking time).
The effect of a LiPA intervention on fasting blood glucose	Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).	Measurement of any changes in fasting blood glucose.
The effect of a LiPA intervention on HbA1c.	Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).	Measurement of any changes in HbA1c.
The effect of a LiPA intervention on total cholesterol.	Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).	Measurement of any changes in total cholesterol.
The effect of a LiPA intervention on HDL- and LDL-cholesterol.	Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).	Measurement of any changes in HDL- and LDL-cholesterol.
The effect of a LiPA intervention on glucose lowering medication.	Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).	Measurement of any changes in glucose lowering medication.
The effect of a LiPA intervention on hip -circumference in cm.	Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).	Measurement of any changes in hip -circumference
The effect of a LiPA intervention program on immune cells.	Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).	Measurement of circulating immune cells using flow cytometry from fresh whole blood. In addition, measurement of circulating cytokines to assess the activation state of immune cells, and store immune cells for functional tests.
The effect of a LiPA intervention on quality of life as measured through the Dutch version of the SF-36 questionnaire.	Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).	The SF-36 is a generic and easily self-administered quality of life instrument. The SF-36 questionnaire measures health on eight multi-item dimensions, covering functional status, well-being, and overall evaluation of health. In six of these eight dimensions, participants rate their responses on a three or six point scale. For each dimension, item scores are coded, summed, and transformed on to a scale from 0 (worst health) to 100 (best health).

Trial Locations

Locations (1)

Maastricht University; 🇳🇱 Maastricht, Netherlands