RE-inventing Strategies for Healthy Ageing; Recommendations and Tools (RESTART) - a Randomized Controlled Trial Testing a Complex Lifestyle Intervention in Older Adults at Increased Risk for Cardiometabolic Disease
Phase: NA
Conditions: Lifestyle, Healthy, Muscle Weakness, Abdominal Obesity, Cardiometabolic Syndrome, Self Efficacy, Diet, Healthy
Sponsor: University of Tromso

 
 
 
 
 
 
 
RE-inventing Strategies for Healthy Ageing; 
Recommendations and Tools (RESTART) - a Randomized 
Controlled Trial Testing a Complex Lifestyle Intervention in 
Older Adults at Increased Risk for Cardiometabolic 
Disease 
 
Study protocol and statistical analysis plan 
 
NCT number: NCT06122441 
Document version: March 10, 2025 
 
 

Project overview 
The goal of the RESTART RCT is to examine whether a complex lifestyle intervention, coordinated 
with municipal and non-government organizations (NGO), can establish and preserve 
improvements in risk factors and functional capacity among older adults at high risk of 
cardiometabolic disease. The main objectives to investigate are whether a complex lifestyle 
intervention, compared to an active control group, will at 24 months have: 
 
Produced a clinically relevant increase in cardiorespiratory ﬁtness (primary endpoint) 
 
Increased muscle strength and power, physical activity and reduced adiposity 
 
Improved body composition, health-related quality of life and cognitive function 
All participants (Control and Intervention Groups) are provided with wrist-worn activity trackers 
at baseline and access to national recommendations on physical activity. The intervention group 
additionally advances through a comprehensive lifestyle program including high-intensity 
aerobic and strength exercise, dietary and behavioral counselling. Intervention participants are 
gradually transitioned into exercise activities organized by Tromsø Municipaity and local NGO:s. 
Testing of outcomes are performed at baseline, 6, 12 and 24 months. Primary endpoint 
(VO2max) is assessed at 24 months. 
 
Detailed description 
The proportion of older individuals worldwide is growing, posing a signiﬁcant challenge to 
western societies. To address the health challenges of the aging population, primary prevention 
eƯorts should focus on various lifestyle factors simultaneously. However, many interventions fail 
to maintain improved lifestyle habits among participants, highlighting the need for novel and 
complex approaches to ensure healthy aging among older adults. 
The RESTART randomized controlled trial aims to investigate whether participants undergoing a 
complex lifestyle intervention improve their cardiorespiratory ﬁtness, muscle strength, physical 
activity, adiposity and body composition, quality of life and cognitive function at 24 months, 
compared to active controls. 
The study and data collection will occur in Tromsø, Norway (pop. 77,000). Participants will 
receive the intervention at a local community exercise center near the University of Tromsø 
campus area. Testing of physical performance will take place at the UiT Faculty of Health 
Sciences research laboratory for sports, physical activity, and public health. The Clinical Trial 
Unit (CTU) at the local university hospital will additionally oversee clinical examinations, 
collection of questionnaire data, and blood sampling. 
At baseline, both the Control and Intervention Groups are given wrist-worn activity trackers and 
access to national physical activity recommendations. The Intervention Group also undergoes a 
comprehensive lifestyle program that includes high-intensity aerobic and strength exercises, as 
well as dietary and behavioral counseling. The Intervention Group is gradually introduced to 
exercise activities organized by Tromsø Municipality and local NGOs. Outcome testing is 
conducted at baseline, 6, 12, and 24 months, with the primary endpoint (VO2max) assessed at 
24 months. 
Intervention participants will be divided into 4 groups of 12-15 participants each and perform 
high-intensity training to target the cardiovascular system and skeletal muscle force-generating 

capacity. For 12 months, the intervention group performs supervised indoor cycling or outdoor 
hill interval training twice a week at a relatively high intensity (≥85% of maximal heart rate during 
4x4 minutes) separated by active rest periods at approximately 70% of maximal heart rate. 
Immediately after the aerobic exercise, participants perform strength training (3 sets of 5 
repetitions) involving leg-press, lateral pull-down, and chest press exercises, with an intensity 
corresponding to ≥80% of their maximal strength. From months 6-12, one of the two weekly 
exercise sessions will be led by the Healthy Life Center (HLC; "Frisklivssentralen"), enabling a 
transition to supervised exercise via the Tromsø municipality primary health care. Between 
month 12-18, the HLC continue to supervise the participants during one weekly exercise 
sessions, while they are additionally introduced to exercise activities arranged by local NGO:s. 
From month 3 to 12, participants will receive behavioral counseling based on the Acceptance 
and Commitment Therapy (ACT) approach during six 2-hour group sessions. The individual 
approach aims to enhance participants' capacity to manage challenging cognitive and 
emotional experiences, foster psychological ﬂexibility and distress tolerance skills, and promote 
the development of self-eƯicacy and new behavior patterns that align with their life values. 
From month 6 to 12, the intervention group will receive four dietary counseling sessions based 
on Norwegian nutritional guidelines. Two individual sessions will involve food diaries, while two 
group sessions with a partner will focus on basic nutritional information and practical food 
preparation. The objective is to promote a healthy, sustainable, and personalized diet while 
promoting increased protein intake, reducing the consumption of high-energy-dense foods and 
drinks with low nutritional value. 
From month 12 and onwards, the intervention group will be granted access to the Re-start eTool 
(https://re-start.no/), which is speciﬁcally tailored to older adults. The eTool oƯers concise and 
easy-to-understand articles, videos, and self-assessment tools that promote physical activity, 
healthy dietary habits, and behavioral strategies from the complex intervention. The Re-start 
eTool aims to provide support and reminders to participants as they gradually transition to 
independently maintaining the achieved lifestyle habits and physical capacity levels. 
Throughout the study period, the intervention instructors and assessors monitor potential 
adverse events during the exercise and testing phases, and all adverse events are reported to the 
study coordinator. Measures to mitigate adverse events include: 1) insurance of participants via 
The Norwegian System of Patient Injury Compensation; 2) involving a MD with sports medicine 
specialization to ensure treatment of potential injuries; 3) pilot study experiences show that 
short-term alternative exercises are eƯective in managing exercise-induced pain and 
discomfort. 
 

 
 
Outcomes 
The primary endpoint is change from baseline in mean V̇ O2max (ml∙kg-1∙min-1) at 24 months. 
Secondary endpoints are change from baseline in mean muscle strength (kg) and mean waist 
circumference (cm) at 24 months. Tertiary endpoints are change from baseline in mean body 
composition (appendicular lean mass [g], fat percentage [%], visceral fat [g]), health-related 
quality of life and cognitive function at 24 months. 
Study period
Enrolment
Allocation
Post-allocation
Close-
out 
TIMEPOINT
-6m
0 
(Baseline) 
6m
12m
18m
24ma
Enrolment:
Eligibility screen
×
×
Informed consent
×
Allocation
×
Intervention elements:
A. Endurance and strength trainingb
B. ACT - Behavioral counsellingb
C. Dietary counsellingb 
D. eTool for lifestyle promotionb
E. Activity monitorb,c,d
F. Physical activity 
recommendationsc 
×
Assessments:
V̇ O2max (primary outcome)
×
×
× 
×
Muscle strength and power
×
×
× 
×
WC and body weight
×
×
× 
×
Physical activity (accelerometer)
×
×
× 
×
Physical activity (activity monitor)c
Body composition (DEXA) 
×
× 
×
Cognitive function (DSST)
×
× 
×
Lung function (spirometry)
×
×
HGS, 5-CST
×
× 
×
Blood pressure and resting HR
×
×
× 
×
ECG
×
×
Biological samples:
FT4, TSH
×
Hb, HbA1c, blood lipids, creatinine, 
cystatin C 
×
×
× 
×
CRP, ALAT, ASAT, ALP, 
testosterone, PEth 
×
× 
×
Urine samples
×
×
× 
×
Questionnaires:
Lifestyle, mental health, and 
diseasese 
×
× 
×

Education, income
×
×
Occupational status and medicine 
use 
×
×
× 
×
Social network
×
× 
×
Interview data
× 
×
Health economic evaluation
×
Adverse eventsd
a Time-point for primary outcome assessment  
b Received by the intervention group 
c Received by the control group 
d Monitored continuously  
e Includes assessment of health-related quality of life (EQ-5D-5L), life satisfaction, anxiety and depression, physical 
activity, diet (NORKOST), general self-efficacy, self-compassion, physical activity acceptance and enjoyment, 
emotional and intuitive eating, binge eating episodes, ideal weight, chronic disease, symptoms and complaints, 
medication use, tobacco use, alcohol use, and self-rated health 
ACT; acceptance and commitment therapy, WC; waist circumference, DEXA; dual-energy X-ray absorptiometry, 
DSST; Digit Symbol Substitution Test; HGS; handgrip strength, 5-CST; 5-repetition chair stand test, HR; heart rate, 
ECG; electrocardiogram, FT4; thyroxine, TSH; thyroid-stimulating Hormone, Hb; Hemoglobin, HbA1C; glycated 
hemoglobin, CRP; C-reactive protein, ALAT; alanine aminotransferase, ASAT; aspartate aminotransferase, ALP; 
alkaline phosphatase, PEth; phosphatidylethanol 
 
Other outcomes include change from baseline in handgrip strength, chair stand performance, 
perceived self-eƯicacy, satisfaction with life, mental health status, psychological ﬂexibility, and 
self-reported diet and smoking at 24 months. We additionally qualitatively assess self-perceived 
determinants of successful lifestyle change at 24 months and perform a health economic 
evaluation of the intervention after 24 months, and follow-up on time to event for CVD 
(myocardial infarction, stroke), diabetes and mortality at 60 months. 
 
Sample size 
We need 44 participants in each group to detect a 2.0 ml∙kg-1∙min-1 mean group diƯerence in 
V̇ O2max -change (primary endpoint), with an α-level of 0.05, power 80%, and standard deviation 
(SD) of 3.3. These sample sizes also enable detection of the following between-group 
diƯerences: lower body strength of 50 kg (SD=40, power>90%) and waist circumference of 4 cm 
(SD=3.5, power>90%). Expecting an acceptance rate of 30% and an attrition rate of 20%, 353 
individuals will be invited and a total number of 110 participants will be block randomized into 
the intervention and active control groups.   
 
Statistical analysis plan 
We will do intention-to-treat analysis and use linear mixed models to assess eƯects on all 
outcomes. Linear mixed models let us include all available information for participants who 
drop out of the trial under the assumption that missing are missing at random. In a sensitivity 
analysis we will exclude dropouts and use per-protocol analyses.