Full Study title: Study Investigating the effects of Alpha-melanocyte stimulatory hormone (alpha-MSH) on reducing blood sugar levels

Eligibility to take part

Inclusion Criteria

1. 18-50 years age
2. Type 1 diabetes with low/undetectable c-peptide
3. BMI 18-30

What will I be asked to do?
Screening will be performed to confirm that patients meet the inclusion criteria for the study. During this session, the purpose of this study will be fully explained. All questions will be answered, and consent obtained before any procedures are performed. The screening visit will include:

• • Informed consent
• • Medical history and physical examination
• • Measurement of height and weight
• • Measurement of vital signs (blood pressure, heart rate)
• • Electrocardiogram (ECG)
• • Blood sampling (including full blood count, urea and electrolytes, liver function tests, glucose, C-peptide, thyroid function test, HbA1c). Samples will be assayed in the clinical laboratories at Imperial College Healthcare NHS Trust.
• • Pregnancy test for females. If positive, they will be excluded from the study. • Bio-electrical impedance analysis to calculate body composition

Participants will be asked to refrain from alcohol and strenuous physical activity for 48 hours before the study. They will also be asked to consume a standardised meal the evening before the study and only consume fluids from 10pm onwards. Participants will attend the Imperial NIHR clinical research facility on the day of the visit. Two venous catheters will be inserted. The first cannula will be used for infusions and the other for blood sampling. Female participants will be studied in the follicular stage of their menstrual cycle.

The sequence of work-up of each study visit will be as per below:

• • Pregnancy test for females. If positive, they will be excluded from the study.
• • Anthropometric Measurements (height, weight, body composition using bioimpedance)
• • Record medications and any changes in health
• • Cannulation
• • Infusion of study solution (α-MSH at one of three concentrations or saline)
• • Oral Glucose Tolerance Test (OGTT)
• • Visual analogue scale for nausea, malaise and facial flushing during the infusion

The saline visit will involve infusion of pharmaceutical GMP-grade sterile 0.5% human albumin (dissolved in saline) obtained from Imperial College Healthcare NHS Trust. Peptides solutions will be made up with 0.5% human albumin dissolved in saline. To reduce binding of peptides to infusion lines, 0.5% human albumin dissolved in saline will be used to prime the infusion lines prior to infusion of the peptides or placebo solutions. α-MSH will be dissolved in 0.9% saline containing 0.5% human albumin to reduce adsorption to the syringe and tubing. The participants will be cannulated then allowed to rest for 30 minutes, after which they will receive an infusion of either saline or α-MSH. Thirty minutes after the infusion has started patients will undergo a standard oral glucose tolerance test: they will be asked to consume a liquid containing 75g glucose within 5 minutes. After the 210 minute infusion has ceased, the participants will remained cannulated for an additional 30 minutes where a final sample will be drawn, and the participant discharged. Blood samples will be collected, and visual analogue scales recorded at the following time points relative to initiation of infusion: -30, 0, 15, 30, 60, 90, 120, 150, 180 minutes.

Who is running this study?
The study is sponsored by Imperial College London and funded by the Obesity Research Fund. The Chief Investigator is Professor Alex Miras

Study location

Hammersmith Hospital