Light Intensity Physical Activity Trial
Condition: Diabetes Mellitus; Physical Exercise; Light Intensity Physical Activity; Arterial Stiffness; Aortic Stiffness; Pulse Wave Velocity; Type2 Diabetes; Sedentary Lifestyle; Artery Disease; Physical Activity
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional

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.
    

Intervention name(s): Interactive workshops LiPAT intervention group; Wrist-worn feedback physical activity monitor; Smartphone application LiPAT; Telephone Coaching; Workshops control group LiPAT
Intervention type(s): Behavioral; Device; Device; Behavioral; Behavioral
Intervention description(s): Workshops include practical behavior change strategies and address barriers to movement, awareness of the immediate benefits of movement and implementation-intentions. Participants will be encouraged to cultivate a learning mind-set in order to better tolerate potential set-backs and to apply strategies such as pre-planning their week to incorporate physical activity, engaging their social network, and setting up systems and habits. Participants' progress in changing their physical activity patterns which will be compared and discussed.; Participants receive the feedback monitor (Fitbit inspire®; commercially available consumer product (https://www.fitbit.com/inspire); With a cloud-based platform the iHealth data is synchronized with a mobile phone app developed by the research team. The app is designed to help the participant to self-monitor their physical activity levels and includes information on total activity and number of steps taken.; participants in the intervention group will receive telephone coaching during the first 3 months of the intervention. Telephone coaching will be conducted twice in the first month and once each in months two and three. The researcher will enquire about the progress with increasing LiPA, about the experiences of applying the strategies discussed during workshops, and about the experience with Fitbit Inspire® and the corresponding app. If needed, the coach will offer suggestions to improve goal adherence.; During the first 6 months of the study (the intervention period) participants in the control group will attend 4 workshops in which the benefits of physical activity and the health-risks of sedentary behavior will be discussed. Additionally, information will be provided on healthy lifestyle for patients with type 2 diabetes.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The study consists of an intervention group and a control group. Both arms run parallel and both groups are measured at the same time points.
Masking: Single (Investigator)
Primary purpose: Prevention
Keywords: Diabetes mellitus; Type2 Diabetes; Sedentary Lifestyle; Physical Activity; Pulse wave velocity; arterial stiffness; aortic stiffness; artery disease; light intensity physical activity