Inclusion criteria

1. Both sexes.

2. Patients with CP aged 20 years or more. Diagnosis for CP will be based on the current Japanese guidelines.1

3. Aetiologies and disease severity for CP are not limited.

Exclusion criteria

1. patients with severe depression or psychiatric disorder such as those with high scores in Patient Health Questionnaire-9 score (10 points or more)25;

2. patients with acute pancreatitis or those with such severe CP that participation in this study is anticipated to be difficult;

3. patients with severe underlying diseases such as advanced malignancies (including pancreatic cancer), severe infectious diseases, severe chronic heart failure and respiratory disorders;

4. pregnant or lactating female subjects;

5. patients who may be at a risk of falls;

6. patients who were judged not to be suitable for the study subjects from the perspective of the ability to participate in PE (such as those with difficulty in walking or exercise);

7. patients with history of surgery or endoscopic therapy for pancreatic diseases;

8. patients with severe pancreatic ascites or pseudocyst;

9. patients who are considered to be unsuitable for study subjects for other reasons.

Study design: non-double-blind randomised controlled trial

Our study participants are patients with CP. All CP stages (compensated, transitional, and decompensated) will be included. Pharmacotherapy and diet therapy for CP will be allowed. Study participants will be randomised into two groups: (1) the PE group and (2) the control group (regular observation group) (figure 1).

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Figure 1

Study design.

Physical exercise

In the PE group, guidance for PE will be provided for each participant once a month at the outpatient guidance clinic. In the PE group, participants will also be instructed to perform exercises with >3 metabolic equivalents (mets; energy consumption in physical activities/resting metabolic rate) for 60 min/day and to perform exercises >23 mets per week.8–13 In the PE group, physical activities equivalent to or higher than walking for 60 min/day should be strongly recommended. We will explain to the control group patients to do the same daily life as that before the trial participation. In both groups, pharmacotherapy such as protease inhibitors and pancreatic enzyme replacement therapy and diet therapy such as fat restriction diet in each underlying pancreatic disease will be allowed and we will ask all study participants for self-declare of daily amount of exercise.1 Direct monitoring for exercise will not be undertaken.

Evaluation using actigram

Actigram is a medical device for gathering objective sleep/awake data in the natural sleeping surroundings over an extended time period.15 16 26 27 The study subjects will be advised to wear a wrist actigram on their non-dominant wrist over a period of 3 days based on the manufacturer’s information.15 16 26 27 Evaluation by actigram will be carried out every 4 weeks. The follow-up period in each subject will be 12 months. At the same time points, data for laboratory testing, questionnaire, and clinical symptoms will be also gathered. Principally, study subjects will be advised to visit our hospital in an outpatient basis.

Data in the actigram will be downloaded into a dedicated computer program. The following five sleep-related factors will be used for assessment as mentioned elsewhere: (1) sleep onset latency; (2) wake after sleep onset (defined as the minutes awake during the sleep period after the beginning of sleep (the first two continuous minutes scored as sleep)); (3) activity index (average amount of activity in sleep); (4) wake episodes (total number of wake counts between trying to start to sleep and wake-up times); and (5) sleep episodes in daytime (total number of sleep counts in daytime).16 The increase in each score suggests the worse sleep quality. Activity index will be assessed as a primary outcome measure as it can well reflect sleep quality.16 A representative case in actigram is presented in figure 2.

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Figure 2

Representative case in actigram. Black thin line indicates activity level, red bold line indicates sleeping state and light blue rectangle indicates time in bed.

Study endpoints

Follow-up and standard of care

During the observation period and after the end of this study, all patients will be seen in the clinic every 4 weeks to address complications of CP and other comorbidities. Compliance with pharmacotherapy will be particularly checked. Regular laboratory tests (haematology, biochemistry, and coagulation) will be needed at the study entry and at the end of study, and on an as-required basis.

Case registration period

From October 2017 to March 2021.

Data collection

A study assistant will gather data elements from patient medical records, including:

Baseline data:

1. sex and age

2. height and body weight

3. vital signs

4. drinking history and smoking history

5. cause for underlying pancreatic diseases

6. clinical stage of CP (compensated, transitional, or decompensated)

7. previous treatments and medicine

8. comorbid conditions

9. baseline laboratory data

10. presence or absence of ascites on radiologic findings.

Statistical methods

Sample size estimation

Based on our previous data of actigram, supposing that α error (type 1 error) is 0.05, detection power (β) is 0.8, difference in the two groups to be detected measured using actigram is 10, and SD of outcome is 10, the number of necessary cases in both groups will be 17 cases (total of 34 cases) in order to randomly allocate one to one.16 Randomisation will be performed by our dedicated computer. We anticipate that a number of participants may drop out of the study; therefore, a total of 40 participants will be required to confirm our hypothesis.