Condition category
Nutritional, Metabolic, Endocrine
Date applied
26/06/2020
Date assigned
02/07/2020
Last edited
27/08/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Patients with type 1 diabetes and advanced type 2 diabetes commonly have high blood glucose levels after eating. This can injure body organs resulting in complications such as heart attacks, blindness and kidney failure. They require life-long treatment with the hormone insulin. While insulin therapy is effective it can come with significant side-effects like very low sugar levels (hypoglycaemia) and excessive weight gain. Researchers have discovered that a hormone from the brain called alpha melanocyte-stimulating hormone (α-MSH) reduces blood glucose in mice and sheep by making them more sensitive to insulin. Researchers now wish to find out for the first time if this is true in humans. They propose to infuse this hormone and measure blood glucose levels in healthy humans to determine whether α-MSH improves their insulin sensitivity.

Who can participate?
Adults age 18-50 who are healthy with no history of diabetes, who have had a stable body weight for at least 3 months and a BMI of ≥18 < 30 (i.e., not underweight or obese)

What does the study involve?
There are two parts to the study. In part one participants will attend four visits where they will receive an infusion of either α-MSH or saline (saltwater) at one of three concentrations. During the infusion, participants will have their glucose tolerance tested by drinking a cup of water with 75 g of sugar in it. Blood samples will be collected over this time (4 hours).
In the second part of the study, participants will attend two visits where they will receive an infusion of either saline or α-MSH at the concentration found in part one to have the greatest effect on glucose tolerance. As well as the α-MSH infusion, they will also undergo a test that infuses insulin and glucose to very precisely measure the effect of the α-MSH infusion on their insulin sensitivity. Over this time (6 hours) blood samples will be collected. Blood samples will be used to measure blood sugar, insulin, α-MSH, and gut hormones.

What are the possible benefits and risks of participating?
There are no direct benefits to the participants medically. The risks are very low as the alpha-MSH peptide has been used in humans previously and has minimal side effects. Some facial flushing may occur for a few minutes, and potentially some nausea. A physician will be present during the infusion to manage these should they occur.

Where is the study run from?
Imperial College London (UK)

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

Who is funding the study?
Health Research Board (Ireland)

Who is the main contact?
Brett Johnson
b.johnson@imperial.ac.uk

Trial website

Contact information

Type

Public

Primary contact

Mr Brett Johnson

ORCID ID

http://orcid.org/0000-0002-2902-1919

Contact details

Department of Metabolism
Digestion and Reproduction
6th Floor Commonwealth Building
Imperial College London
Hammersmith Hospital
Du Cane Road
London
W12 0NN
United Kingdom
+44 (0)7592589553
Brett.johnson@nhs.net

Type

Scientific

Additional contact

Dr Alex Miras

ORCID ID

http://orcid.org/0000-0003-3830-3173

Contact details

Department of Metabolism
Digestion and Reproduction
6th Floor Commonwealth Building
Imperial College London
Hammersmith Hospital
Du Cane Road
London
W12 0NN
United Kingdom
-
a.miras@nhs.net

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

CPMS 45135, IRAS 275910

Study information

Scientific title

A physiological study of the effect of alpha-MSH on glucose clearance in healthy participants

Acronym

Alpha-MSH

Study hypothesis

Alpha-melanocyte stimulatory hormone (alpha-MSH) is a hormone that is produced by the brain and released into the bloodstream. It has multiple functions in the body, such as reducing inflammation, promoting skin pigmentation and controlling energy balance. It has recently been shown that in animals, infusion of alpha-MSH increases glucose clearance by promoting its uptake in skeletal muscle, thus lowering circulating blood sugar. Human studies to understand this action of alpha-MSH is a critical next step.

This study aims to observe the effect of alpha-MSH on increasing glucose clearance from the blood by promoting its uptake into skeletal muscle in healthy humans.

Hypothesis: Alpha-melanocyte stimulating hormone improves post-prandial glucose clearance versus saline.

Ethics approval

Approved 19/05/2020, London - Fulham Research Ethic Committee (Barlow House, 3rd Floor, 4 Minshull Street, Manchester, M1 3DZ, UK; +44 (0)2071048235; fulham.rec@hra.nhs.uk), REC ref: 20/LO/0355

Study design

Randomised; Both; Design type: Not Specified, Not Specified, Cross-sectional

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

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

Condition

Glucose clearance from the blood

Intervention

For this prospective double-blinded (both the researchers and study participants are unaware of the intervention) randomised control trial (RCT) the researchers plan to recruit 15 healthy volunteers from the general public. The participants will be healthy male and female volunteers (we aim to recruit 8 males and 7 females) above the age of 18 with no major medical conditions.

Prior to being accepted into the study, participants will first be screened by a member of the research team to ensure they meet the inclusion and exclusion criteria. At this screening visit, participants will be informed about the study and have the opportunity to ask questions. They will be given a detailed participant information sheet which they may keep to review. Once the participant has been given a minimum of 24 hours to consider their entry into the study, informed consent in person will be obtained.

Every participant will then attend 4 separate morning visits at Hammersmith Hospital after an overnight fast (fasted since 10 pm the night before). Each visit will last approximately 4 hours and take place at a minimum of 1-week intervals. At each of these visits the participants will be randomised (assigned at random by a computer programme) to infusions of one of three doses of alpha-MSH or placebo (normal saline - 0.9% sodium chloride (salt) solution). These infusions will last for 150 minutes and will be delivered through an intravenous cannula placed in the arm. A second cannula will be inserted into the other arm to enable extraction of blood samples. Thirty minutes after each infusion begins, participants will be asked to consume a sugary drink which will raise their blood sugar levels. Throughout the infusion, blood will be drawn and circulating blood glucose measured. This will allow the researchers to measure the body’s response to glucose under each of the doses and compare this to the placebo in order to identify the dose at which alpha-MSH acts to reduce blood sugar.

Once all participants have completed four infusion visits (three doses of alpha-MSH and one placebo visit) with oral glucose tolerance tests, they will be invited back for a further two morning fasted visits at Hammersmith Hospital. Each visit will last approximately 4 hours, during which participants will undergo what is known as a 'glucose clamp' where their blood glucose is maintained at a stable level during an infusion of insulin with alpha-MSH or placebo. The participant will require three separate intravenous lines (one for insulin, one for either alpha MSH or placebo and one for extracting blood samples). During one of these visits, the dose of alpha-MSH administered will be that which is observed to cause the greatest change in blood glucose levels during the glucose tolerance test visits. In the other visit, saline will be administered as placebo. At the first of these two visits, the participant will be randomised to alpha-MSH or placebo, with the second visit administering the infusion not given in the first. Both the researchers and participant will be unaware of the treatment during these visits. This glucose clamp technique will allow the researchers to quantify the amount of glucose that is being used by the body in response to an infusion of alpha-MSH. The study will conclude when participants complete two glucose clamp visits.

If any of the expected side effects (nausea, facial flushing, general discomfort) are present at any dose they will be assessed via the Visual Analogue Scale provided, where the participant will rate each sensation by marking with a dash along a 10 cm line.

The blood collected throughout the infusions will be analysed in the lab for relevant hormones and proteins.

Intervention type

Drug

Phase

Not Applicable

Drug names

Alpha-MSH

Primary outcome measure

1. Area under the curve of glucose concentration measured using blood tests at an OGTT during saline vs. alpha-MSH infusion visits at 0-180 minutes
2. Glucose infusion rate measured using blood tests at the euglycaemic hyperinsulinaemic clamp during saline vs. alpha-MSH infusion visits at 0-240 minutes

Secondary outcome measures

1. Area under the curve for the following metabolites during OGTT and clamp during saline or alpha-MSH infusion visits at 0-180 minutes:
1.1. Insulin measured using blood tests
1.2. C-peptide measured using blood tests
1.3. Glucagon measured using blood tests
1.4. GLP-1 measured using blood tests
1.5. α-MSH measured using blood tests
2. Adverse events (including flushing) as reported by the participant using visual analogue scales at -30 to 180 minutes

Overall trial start date

05/05/2019

Overall trial end date

31/07/2021

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. 18-50 years old
2. Normal fasting glucose (< 5.6 mmol/l)
3. Stable body weight for at least 3 months
4. BMI > = 18 < 30 kg/m²
5. The participant is capable of giving written informed consent
6. The participant is able to read, comprehend and record information written in English

Participant type

Healthy volunteer

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 15; UK Sample Size: 15

Participant exclusion criteria

1. Previous or current psychiatric diagnosis listed in DSM-V Axis 1
2. Significant current or past medical or psychiatric history that, in the opinion of the investigators, contraindicates their participation
3. History of type 1 or type 2 diabetes mellitus
4. History of endocrine disorder
5. History of ischaemic heart disease, hypertension, heart failure, cardiac arrhythmia, peripheral vascular or cerebrovascular disease.
6. History or presence of significant respiratory, gastrointestinal, hepatic, oncological, neurological or renal disease or other condition that in the opinion of the Investigators may affect participant safety or outcome measures
7. Unwillingness or inability to follow the procedures outlined in the protocol
8. History of sensitivity to any of the peptides, or components thereof, or a history of drug or other allergy that, in the opinion of the investigators, contraindicates their participation
9. Use of current regular prescription or over-the-counter medications that in the opinion of the Investigators may affect participant safety or outcome measures
10. Clinically significant abnormalities in screening electrocardiogram (ECG) or blood tests abnormalities which in the opinion of the study physician, is clinically significant and represents a safety risk
11. Current pregnancy or breast-feeding in female participants (the Investigators would advise on using contraception for the duration of the visits)
12. Pulse rate < 40 or > 100 beats per minute OR systolic blood pressure > 160 and < 100 and a diastolic blood pressure > 95 and < 50 in the semi-supine position
13. The participant has participated in a clinical trial and has received an investigational product within the following time period prior to the first experimental visit in the current study: 90 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer)
14. Exposure to more than 3 new investigational medicinal products within 12 months prior to the screening
15. Participants who have donated, or intend to donate, blood within three months before the screening visit or following study visit completion

Recruitment start date

15/09/2020

Recruitment end date

28/02/2021

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Imperial College Healthcare NHS Trust
St. Marys Hospital Praed Street
London
W2 1NY
United Kingdom

Trial participating centre

Imperial College London
Investigative Medicine Du Cane Road
London
W12 0NN
United Kingdom

Sponsor information

Organisation

Imperial College London

Sponsor details

c/o Keith Boland
Clinical Trials Manager
Room 221
Level 2
Medical School Building
Norfolk Place
London
W2 1PG
United Kingdom
+44 (0)20 7594 9480
k.boland@imperial.ac.uk

Sponsor type

University/education

Website

http://www3.imperial.ac.uk/

Funders

Funder type

Government

Funder name

Health Research Board (Republic of Ireland); Grant Codes: ILP-HSR-2017-007

Alternative name(s)

THE HEALTH RESEARCH BOARD, HRB

Funding Body Type

government organisation

Funding Body Subtype

Local government

Location

Ireland

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal. No additional files currently available.

IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

01/07/2022

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

27/08/2020: The recruitment start date was changed from 01/08/2020 to 15/09/2020. 26/06/2020: Trial's existence confirmed by the NIHR.