Condition category
Nutritional, Metabolic, Endocrine
Date applied
09/07/2020
Date assigned
23/07/2020
Last edited
23/07/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

Plain English Summary

Background and study aims
In people without diabetes, symptoms due to low sugar levels (hypoglycaemia) a few hours after eating is a common problem after weight-loss surgery which can be distressing. Currently, there is no good treatment available for this problem.The altered absorption of glucose from the gut after weight-loss surgery seems to be an important factor contributing to hypoglycemia after the meal.

Studies in animals after weight-loss surgery have demonstrated that increased salt intake with a meal can modify the absorption of glucose from the gut and increase the glucose levels. If this is also the case in humans, increased salt intake with a meal may be a treatment for post-meal hypoglycemia after weight-loss surgery.

Who can participate?
Patients over one year after gastric bypass, aged 18 - 74 years.

What does the study involve?
This study will investigate the effect of increased salt intake with a meal on glucose after weight-loss surgery in patients without diabetes. Participants will be randomised to either
Group 1: Standardised MMTT (mixed meal tolerance test) with 2g of table salt at visit 1, followed by standardised meal without additional table salt at visit 2.
Group 2: Standardised MMTT (mixed meal tolerance test) without 2g table salt at visit 1, followed by standardised meal with additional 2g table salt at visit 2.

What are the possible benefits and risks of participating?
Benefits: Contributing to the scientific understanding of the effects of the intervention. The results of this study may contribute to the design of a potential treatment option to prevent low blood glucose episodes in people who have had weight loss surgery. Potential participants with hypoglycaemia may be identified during the study and will be provided with nutritional advice (after completion of the study.
Risks: Participants may experience symptoms that are related to dumping syndrome and low blood sugar levels (hypoglycaemia). In order to reduce the risk of experiencing these symptoms, people with a diagnosis of hypoglycaemia after weight loss surgery will not be included in the study. The amount of sugar in the set meal will be a lot less compared to the usual meals that would trigger dumping syndrome. Throughout the visits, participants will be monitored at all times for any symptoms related to hypoglycaemia and dumping syndrome through study questionnaires and if low glucose levels are confirmed, the test will be stopped and participants will receive treatment for hypoglycaemia. The clinical team will also be on hand to manage any symptoms that may develop.

Where is the study run from?
Leicester Diabetes Centre (UK)

When is the study starting and how long is it expected to run for?
March 2019 to December 2021

Who is funding the study?
Novo Nordisk UK Research Foundation

Who is the main contact?
Frahim Makda, Frahim.makda@uhl-tr.nhs.uk

Trial website

Contact information

Type

Public

Primary contact

Ms Frahim Makda

ORCID ID

Contact details

Leicester Diabetes Centre
Leicester General Hospital
Gwendolen Road
Leicester
LE5 4PW
United Kingdom
-
frahim.makda@uhl-tr.nhs.uk

Type

Scientific

Additional contact

Dr Dimitris Papamargaritis

ORCID ID

http://orcid.org/0000-0001-5044-1515

Contact details

Leicester Diabetes Centre
Leicester General Hospital
Gwendolen Road
Leicester
LE5 4PW
United Kingdom
+44 (0)1162588973
dp421@le.ac.uk

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

CPMS 45812, IRAS 273999

Study information

Scientific title

The effect of increased sodium intake with a carbohydrate-rich meal on glucose homeostasis in subjects without diabetes after bariatric surgery: A proof-of-concept, randomised, open-label, crossover study

Acronym

The SALT Study

Study hypothesis

Increased sodium intake with a carbohydrate-rich meal in patients without diabetes after RYGB will increase the postprandial and nadir glucose levels after RYGB through a more physiological and gradual absorption of the dietary glucose at the proximal small intestine

Ethics approval

Approved 26/06/2020, Yorkshire & Humber- South Yorkshire Research Ethics Committee (NHSBT Newcastle Blood Donor Centre, Holland Drive, Newcastle upon Tyne, NE2 4NQ, UK; +44 (0)207 104 8091; southyorks.rec@hra.nhs.uk), ref: 20/YH/0177

Study design

Interventional randomized controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Other

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Diabetes

Intervention

This study is a proof-of-concept, randomised, open label, crossover study conducted in male and female participants without diabetes who have undergone Roux-en-Y gastric bypass (RYGB). The objective of the study is to investigate the effect of increased sodium intake with a carbohydrate rich meal on glucose homeostasis in patients without diabetes after bariatric surgery.

Participants will be randomised to one of the following two treatment sequences at baseline:-
• Group 1: will receive a standardised MMTT (mixed meal tolerance test) with 2g of table salt at visit 1, and then a standardised meal without additional table salt at visit 2.
• Group 2: will receive a standardised MMTT (mixed meal tolerance test) without addition of 2g table salt at visit 1, then a set meal with 2g table salt at visit 2.

Standardised MMTT (mixed meal tolerance test) will consist of 170mls of orange juice (Tropicana smooth orange juice, where the 2g of table Salt will be diluted for those on the “additional table Salt” treatment sequence) followed by 135g Blueberry Yoghurt with Granola (Yeo Valley, Blueberry Yoghurt with Crunchy Granola)

Participants will attend a screening (familiarisation) visit prior to the start of the study followed by 2 visits and then a Safety Call.

The first visit (visit 0) is the Screening (Familiarisation) Visit and will occur not more than 14 days nor less than 1 day before the Visit 1 (Baseline visit). Visit 0 (approximately 2 hours) will involve an assessment of inclusion/exclusion criteria, an explanation of study procedures and obtaining verbal and written consent from participants by a trained healthcare professional. In addition, blood will be taken for HbA1c, Full blood count (FBC), renal function and liver function as part of investigation for exclusion criteria. A urine pregnancy test will also take place for all female participants of child bearing potential. These samples will all be processed at the pathology laboratory within the Leicester General Hospital. In addition demographic information, past medical/surgical history, concomitant medication, medication history will also be collected at this visit. A General Physical examination will be performed by a trained delegated clinician.

Visit 1 is the Baseline visit lasting approximately 5 hours and will take place at Leicester Diabetes Centre. Randomisation to one of the two treatment sequences will take place during this visit. Anthropometrics (Weight(including body fat %), Height, BP, Pulse rate) will be measured. Changes in medications since screening will be documented. Urine pregnancy test will be performed in all women of childbearing potential. A cannula will be inserted to allow multiple blood samples collection. Participants randomised to standardised MMTT plus 2g additional table Salt (NaCl) treatment sequence will be asked to drink first 170mls of orange juice with 2g of table Salt (NaCl) diluted into this and then consume 135g of Blueberry Yoghurt with Crunchy Granola (Yeo Valley) under supervision. Participants randomised to standardised MMTT without additional Salt (NaCl) will be asked to drink 170mls of orange juice (without added table Salt) and then consume 135g of Blueberry Yoghurt with Crunchy Granola (Yeo Valley) under supervision. Blood samples will be collected in the fasting state (immediately before MMTT) and at 15’, 30’, 60’, 90’, 120’, 150’ and 180’ after MMTT ingestion for measurement of glucose, insulin, c-peptide and GLP-1. Questionnaires on dumping symptoms as well as questionnaires on hypoglycaemia symptoms will be completed during the MMTT. For the 24 hours before study visits 1 and 2, participants will be asked to refrain from: completing any moderate to vigorous form of physical activity and consuming any alcohol.

Visit 2 (occurs 7 days after visit 1) lasts approximately 5 hours and is similar to visit 1. The only change is that participants who were initially allocated to standardised MMTT plus 2g additional table Salt (NaCl) will now receive the standardised MMTT without additional table salt (NaCl) sequence. Conversely, those who were initially allocated to receive the standardised MMTT without additional table salt, (NaCl) will receive the standardised MMTT with the table salt (NaCl) added. All procedure visits will be the same as Visit 1 and urine pregnancy tests will be performed for all women of childbearing age at visit 2.

Safety Call 1 (occurs 7 days after Visit 2) is a telephone call to the patient. Patient will be asked to report any adverse events between Visit 2 and the day of the Safety Call 1. Safety call 1 is the end of the study.

Intervention type

Other

Phase

Drug names

Primary outcome measure

Nadir (lowest) glucose levels after the standardised mixed meal tolerance test after RYGB measured using blood test in the fasting state (immediately before MMTT) and at 15 min, 30 min, 60 min, 90 min, 120 min, 150 min and 180 min after MMTT ingestion

Secondary outcome measures

Measured using blood test in the fasting state (immediately before MMTT) and at 15 min, 30 min, 60 min, 90 min, 120 min, 150 min and 180 min after MMTT ingestion (unless otherwise stated):
1. Fasting and peak glucose level
2. Insulin level
3. GLP-1 level
4. c-peptide level
5. Sigstad score
6. Edinburgh Hypoglycaemia Scale score
7. Amount of glucose (in grams) needed to restore euglycaemia
8. Number of MMTTs needed to be terminated early because of hypoglycaemia (blood glucose or capillary glucose levels ≤3.0mmol/l) measured using case report forms

Overall trial start date

31/03/2019

Overall trial end date

01/12/2021

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Aged >=18 years old but less than 75 years old
2. Subjects >=1 year after gastric bypass (RYGB)
3. Able to understand written and spoken English
4. Able to give informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 12; UK Sample Size: 12

Participant exclusion criteria

1. Use of any glucose-lowering medication (including insulin)
2. Adrenal insufficiency and/or substitution with glucocorticoids
3. eGFR <=60 ml/min/173m²
4. Recent active infection (an active infection will be any infection over the last 10 days)
5. Current use of steroids
6. Known liver cirrhosis or ALT >2 times above upper normal limit
7. Known primary or secondary hyperaldosteronism
8. Moderate or severe hypertension during screening visit (Systolic Blood Pressure >160mmHg as average of 3 measurements)
9. Established diagnosis of congestive heart failure
10. Significant peripheral oedema on clinical examination at screening visit
11. People with allergy or intolerance to the mixed meal tolerance test (eg, milk protein allergy, lactose and gluten intolerance)
12. People following a vegan diet (mixed meal tolerance test not suitable for those following a vegan diet)
13. Other bariatric procedure except of RYGB
14. Previous revisional bariatric surgery
15. Currently pregnant or breastfeeding
16. Patients with history of Type 1 or Type 2 Diabetes
17. Patients with diagnosis of Epilepsy
18. HbA1C >=65% or >=48 mmol/l at screening blood tests
19. Haemoglobin (Hb) <100 g/l at screening blood tests
20. Participating in another research study involving intervention within 3 months of screening
21. Having a formal previous diagnosis of postprandial hypoglycaemia
22. Being on acarbose, diazoxide, octreotide or other treatment for postprandial hypoglycaemia
23. Any concurrent condition, in the judgment of investigator and/or sponsor, that could interfere with the safety and study conduct or interpretation of study results

Recruitment start date

01/09/2020

Recruitment end date

01/09/2021

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Leicester Diabetes Centre
Leicester General Hospital
Leicester
LE5 4PW
United Kingdom

Sponsor information

Organisation

University of Leicester

Sponsor details

Research Governance Office
Research & Enterprise Division
Leicester
LE5 4PW
United Kingdom
+44 (0)1162584099
rgosponsor@le.ac.uk

Sponsor type

University/education

Website

http://www.le.ac.uk/

Funders

Funder type

Industry

Funder name

Novo Nordisk UK Research Foundation

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

Trusts, charities, foundations (both publically funded and privately funded)

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Any original findings will be published as conference abstracts or as papers in reputable refereed journals. Authorship will include those listed as investigators in the research protocol. These individuals will take personal responsibility for their identified area of expertise and will identify their contributions to the research process in any publication. Collaborators, other contributors, funding bodies, the Sponsor and the authorizing REC will be acknowledged.

IPD sharing statement:
All data generated or analysed during this study will be included in the subsequent results publication.

Intention to publish date

30/06/2022

Participant level data

Other

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

09/07/2020: Trial’s existence confirmed by National Institute for Health Research (NIHR).