UMIN-ICDS Clinical Trial

Public title

A study to examine whether eating cheese before bedtime is effective against low blood glucose during sleep after stomach surgery, and whether the degree of low blood glucose differs by type of surgery

Acronym

Post-gastrectomy LES-CGM study

Scientific Title

Bedtime cheese (late evening snack) intervention for nocturnal hypoglycemia after gastrectomy and comparison among surgical procedures: a prospective interventional study using continuous glucose monitoring

Scientific Title:Acronym

Post-gastrectomy LES-CGM study

Region

Japan

Condition

Nocturnal hypoglycemia after gastrectomy for gastric cancer or esophagogastric junction cancer

Classification by specialty

Endocrinology and Metabolism

Gastrointestinal surgery

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

Asymptomatic nocturnal low glucose is frequently detected by continuous glucose monitoring (CGM) after gastrectomy. In our pilot study, supplementation with a low-carbohydrate, high-fat enteral formula (200 mL twice daily) reduced the time with CGM glucose below 70 mg/dL, but abdominal symptoms such as postprandial abdominal gurgling, lower abdominal bloating, and upper abdominal pain after meals worsened. In this study, patients after gastrectomy wear a CGM sensor for two weeks, and the following two questions are addressed.
(1) Study 1 (observational): to compare CGM-derived nocturnal low glucose exposure (nocturnal time below range, TBR) among surgical procedures (distal, proximal, appetite-preserving, and total gastrectomy). The main comparison is between appetite-preserving gastrectomy (APG) and total gastrectomy. APG, developed in our department for esophagogastric junction cancer or upper gastric cancer confined to the lesser curvature, preserves the ghrelin-producing gastric fundus with its blood supply as an endocrine organ; food passes directly from the esophagus to the jejunum and does not pass through the preserved remnant stomach. Nocturnal TBR is compared between APG, which preserves the ghrelin-producing region, and total gastrectomy, which removes it, with adjustment for differences in patient background and postoperative course.
(2) Study 2 (interventional): to test whether eating a small amount (two pieces, about 34 g) of commercially available processed cheese, which can be bought in ordinary stores, as a late evening snack improves nocturnal TBR, using a within-patient comparison in a crossover design with randomized order.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Developmental phase

Not applicable

Primary outcomes

Nocturnal TBR (percentage of time between 00:00 and 06:00 with CGM glucose below 70 mg/dL).
Study 1: adjusted between-group difference in nocturnal TBR during the control week between the appetite-preserving gastrectomy group and the total gastrectomy group.
Study 2: within-patient difference in nocturnal TBR between the control week and the cheese week (7 nights each).

Key secondary outcomes

Study 1: association between early-morning fasting plasma des-acyl ghrelin and nocturnal TBR; des-acyl ghrelin by surgical procedure; associations of nocturnal heart rate variability with nocturnal TBR, hypoglycemia-like symptoms, and anxiety/depression (analyses of des-acyl ghrelin are exploratory).
Study 2: proportion of patients with nocturnal TBR below 4%; other CGM metrics (24-hour TBR, time in range, time above range, nocturnal mean glucose, coefficient of variation, MAGE); hypoglycemic symptoms (Edinburgh Hypoglycaemia Symptom Scale); gastrointestinal symptoms and quality of life (PGSAS-37); anxiety and depression (HADS); symptom diary items; week-to-week comparison of nocturnal heart rate variability.

Study type

Interventional

Basic design

Cross-over

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

No treatment

Stratification

YES

Dynamic allocation

NO

Institution consideration

Institution is not considered as adjustment factor.

Blocking

YES

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Food

Interventions/Control_1

Cheese-first sequence: on days 1-7, participants eat two pieces (about 34 g; about 110 kcal, 7.0 g protein, 8.8 g fat, 0-1.2 g carbohydrate) of commercially available processed cheese (6P Cheese, Megmilk Snow Brand Co., Ltd.) every night one hour before bedtime, and on the following days 8-14 they eat no cheese (control week). CGM is worn continuously for all 14 days.

Interventions/Control_2

Control-first sequence: on days 1-7, participants eat no cheese (control week), and on the following days 8-14 they eat the same two pieces of cheese as in arm 1 every night one hour before bedtime. CGM is worn continuously for all 14 days.

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

85

years-old

>=

Gender

Male and Female

Key inclusion criteria

Patients who meet all of the following:
1) Underwent distal, proximal, appetite-preserving, or total gastrectomy for gastric cancer (C16) or esophagogastric junction cancer (C15)
2) Three months to five years after surgery at enrollment, with stable general condition (ECOG performance status 0-1)
3) Aged 20 to 85 years at enrollment
4) Able to manage CGM wear, the symptom diary, and cheese intake independently, with written informed consent obtained from the patient

Key exclusion criteria

Patients who meet any of the following:
1) Receiving pharmacological treatment for diabetes (oral hypoglycemic agents or insulin); patients managed by diet alone are not excluded
2) Currently receiving chemotherapy (patients who have completed adjuvant chemotherapy are eligible)
3) Active malignancy or recurrence (patients with no evidence of disease after treatment and no recurrence at enrollment are not excluded)
4) Severe hepatic or renal dysfunction (including dialysis)
5) Unable to eat the study food because of milk or dairy allergy or similar reasons
6) Unable to wear the CGM sensor because of skin disease, adhesive allergy, or similar reasons
7) Pregnant or breastfeeding
8) Unable to give consent or to manage the diary and cheese intake independently because of cognitive decline or similar reasons
9) After local resection or surgery for remnant gastric cancer (including reoperation with completion gastrectomy)
10) Regular use of enteral formula or other nutritional supplements that cannot be stopped during the measurement period
11) Any other condition judged inappropriate by the principal investigator or a co-investigator

Target sample size

140

Name of lead principal investigator

1st name	Naoki
Middle name
Last name	Hiki

Organization

Kitasato University School of Medicine

Division name

Department of Upper Gastrointestinal Surgery

Zip code

252-0374

Address

1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa

TEL

042-778-8111

Email

nhiki@med.kitasato-u.ac.jp

Name of contact person

1st name	Shohei
Middle name
Last name	Fujita

Organization

Kitasato University School of Medicine

Division name

Department of Upper Gastrointestinal Surgery

Zip code

252-0374

Address

1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa

TEL

042-778-8111

Homepage URL

Email

fujita.shohei@kitasato-u.ac.jp

Institute

Kitasato University

Institute

Department

Personal name

Organization

Kitasato University

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Ethics Committee of Kitasato University School of Medicine and Hospital

Address

1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa

Tel

042-778-8111

Email

rinrib@med.kitasato-u.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

北里大学病院

Date of disclosure of the study information

2026

Year

09

Month

24

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

Individual participant data will not be shared.

IPD sharing Plan description

Participants were not informed that their individual data would be provided externally. Any secondary use will require a new research protocol approved by the ethics committee.

Recruitment status

Preinitiation

Date of protocol fixation

2026

Year

08

Month

28

Day

Date of IRB

2026

Year

09

Month

16

Day

Anticipated trial start date

2026

Year

11

Month

01

Day

Last follow-up date

2029

Year

01

Month

14

Day

Date of closure to data entry

2029

Year

02

Month

28

Day

Date trial data considered complete

2029

Year

03

Month

31

Day

Date analysis concluded

2029

Year

09

Month

30

Day

Other related information

The two weeks are measured consecutively without a washout period, because the effect of a late evening snack is expected to be temporary and confined mainly to the night of intake, making carryover into the following week unlikely. Carryover is assessed in an analysis that includes period and sequence.
Two manuscripts (Study 1 and Study 2) will be prepared from the same two-week measurement. Both will state that they use the same cohort, cite each other, and will not report the same primary results twice.

Registered date

2026

Year

09

Month

24

Day

Last modified on

2026

Year

09

Month

24

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000072164