Does an infusion of alpha-melanocyte stimulating hormone reduce blood sugar after a sugary drink in healthy people and those with type 1 diabetes mellitus?

Trial ID: ISRCTN26265036

Other - Phase Unknown - No longer available

Current plain English summary as of 19/11/2021: 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? In parts one and two of the study, adults aged 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) will be eligible to take part. In part three the study will recruit adults aged 18-50 who have type 1 diabetes mellitus but are otherwise healthy, 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 three parts to the study. In part one, healthy 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). Then 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. In part two, healthy participants will attend two visits where they will undergo glucose tolerance tests as described above while receiving an infusion of either high dose alpha-MSH or saline. In part three, participants with type 1 diabetes mellitus attend two visits where they will undergo glucose tolerance tests as described above while receiving an infusion of either high dose alpha-MSH or saline. 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) and Ulster University (UK) When is the study starting and how long is it expected to run for? May 2019 to December 2024 Who is funding the study? Investigator initiated and funded Who is the main contact? Brett Johnson brett.johnson@nhs.net Previous 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 2022 Who is funding the study? Investigator initiated and funded Who is the main contact? Brett Johnson b.johnson@imperial.ac.uk

Conditions

• Glucose clearance from the blood
• Nutritional, Metabolic, Endocrine

Interventions

• Alpha-MSH

Eligibility

Inclusion criteria

• Current participant inclusion criteria as of 19/11/2021: Work Package 1 and 2: 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 and <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 Work Package 3: 1. 18-50 years old 2. Diagnosis of T1DM with low/undetectable plasma C-peptide 3. Stable body weight for at least 3 months 4. BMI ≥18 and <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 Previous 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

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

Sponsor

Imperial College London

Source: https://www.isrctn.com/

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