Clinical trial NCT03415880: Light Intensity Physical Activity Trial
Official title: The Light Intensity Physical Activity Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Mellitus
Physical Exercise
Light Intensity Physical Activity
Arterial Stiffness
Aortic Stiffness
Pulse Wave Velocity
Type2 Diabetes
Sedentary Lifestyle
Artery Disease
Physical Activity
Keywords: Diabetes mellitus
Type2 Diabetes
Sedentary Lifestyle
Physical Activity
Pulse wave velocity
arterial stiffness
aortic stiffness
artery disease
light intensity physical activity
Lead sponsor: Academisch Ziekenhuis Maastricht
Sponsor class: OTHER
Collaborators: name: European Foundation for the Study of Diabetes
First posted: 2018-01-30
Enrollment: 132
Sex: ALL
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: PREVENTION

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.

Eligibility criteria: 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)

Primary outcomes:
measure: The effect of a LiPA intervention program on reducing aortic carotid-to-femoral pulse-wave velocity (PWV) in patients with type 2 diabetes.
timeFrame: Change from baseline PWV at 6 months.
measure: The effect of a LiPA intervention program on increasing carotid distensibility in patients with type 2 diabetes.
timeFrame: Change from baseline carotid distensibility at 6 months.
Secondary outcomes:
measure: Feasibility of a LiPA intervention program on reducing sedentary time as measured by activPAL
timeFrame: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).
measure: The effect of a LiPA intervention on changes in blood pressure.
timeFrame: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).
measure: The effect of a LiPA intervention on waist -circumference in cm.
timeFrame: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).
measure: The effect of a LiPA intervention on quality of life as measured through the Dutch versions of the EQ-5D questionnaire.
timeFrame: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).
measure: 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).
timeFrame: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).
measure: Feasibility of a LiPA intervention program on increasing standing and stepping time as measured by activPAL.
timeFrame: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).
measure: The effect of a LiPA intervention on fasting blood glucose
timeFrame: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).
measure: The effect of a LiPA intervention on HbA1c.
timeFrame: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).
measure: The effect of a LiPA intervention on total cholesterol.
timeFrame: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).
measure: The effect of a LiPA intervention on HDL- and LDL-cholesterol.
timeFrame: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).
measure: The effect of a LiPA intervention on triglycerides.
timeFrame: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).
measure: The effect of a LiPA intervention on glucose lowering medication.
timeFrame: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).
measure: The effect of a LiPA intervention on hip -circumference in cm.
timeFrame: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).
measure: The effect of a LiPA intervention on body composition
timeFrame: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).
measure: The effect of a LiPA intervention on quality of life as measured through the Dutch version of the SF-36 questionnaire.
timeFrame: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).
measure: The effect of a LiPA intervention program on immune cells.
timeFrame: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).
measure: The effect of a LiPA intervention program on microvascular function
timeFrame: Measured at baseline (t=0), after month 3 (t=3), month 6 (t=6) and 12 months after baseline (t=12).
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University
Study officials:
affiliation: Academisch Ziekenhuis Maastricht
name: Coen D Stehouwer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Maastricht University
name: Annemarie Koster, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Academisch Ziekenhuis Maastricht
name: Ronald M Henry, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: