How do hormones affect reproduction and metabolism in people with type 2 diabetes and people who do not have type 2 diabetes?
| ISRCTN | ISRCTN10114288 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN10114288 |
| Secondary identifying numbers | 16HH3156; CPMS 20865 |
- Submission date
- 29/11/2019
- Registration date
- 09/12/2019
- Last edited
- 26/02/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English Summary
Background and study aims
Up to 40% of people who are obese and/or have type 2 diabetes have low reproductive hormone levels (hypogonadism) and therefore have reduced sexual function and reduced fertility. Also, having low reproductive hormone levels is associated with lower insulin secretion and higher insulin resistance in people with type 2 diabetes. Some hormones have been shown to be essential for fertility in animals and humans, whilst other hormones have been shown to affect the amount of insulin produced, appetite and body weight in animals and humans (but some of these effects might be different in different genders). Identifying hormones that can control both reproduction and metabolism may lead to better treatments for fertility disorders.
Aims
Part A of the study will investigate if hormones, which are known to affect insulin and food intake and are produced in the gut (i.e. glucagon, glucagon-like peptide-1, oxyntomodulin, peptide-YY and substance P) can affect reproductive hormones.
Part B will investigate if certain reproductive hormones (i.e. kisspeptin and neurokinin B) can improve the ability of the body to respond to glucose how these hormones affect appetite, the quantity of food eaten and how much energy people use.
Who can participate?
Men and women aged 18 – 60 years who are obese and/or have type 2 diabetes and are non-smokers.
What does the study involve?
People will only be allowed to take part in both parts of the study at the same time.
In Part A, people who participate will come to the research facility for up to six visits. During one visit they will be given salty water through a plastic tube placed in a vein and during each of the other visits they will receive (through a plastic tube placed in a vein) a different hormone produced by the gut, which has been dissolved in salty water. The study visits will take place in a random order. During all study visits, blood samples will be taken (to measure hormone, glucose and insulin levels) through a plastic tube placed in a different vein.
In Part B, people who participate will come to the research facility for up to three pairs of visits. They will be asked to fast overnight before each study visit. For each pair of study visits, during one visit they will be given kisspeptin or neurokinin B (through a plastic tube placed in a vein) and salty water (through a plastic tube placed in a vein) on the other study visit. During one pair of study visits, they will be asked to drink a sugary drink. During the second pair of study visits, they will be given a sugar solution into a vein (via a plastic tube) with a small dose of insulin given to some people. During the third pair of study visits, they will be asked to rate their hunger levels, they will be given a meal to eat and in some cases measurements of how much energy they are using will be performed. During all study visits, blood samples will be taken (to measure hormone, glucose and insulin levels) through a plastic tube placed in a different vein.
What are the possible benefits and risks of participating?
BENEFITS - The information that we get from this study will help us to understand how to treat patients who suffer from type 2 diabetes, obesity and/or fertility problems.
RISKS - It is possible that mild nausea may occur. The insertion of the cannula may cause minor discomfort or superficial bruising. Some gut hormones can affect blood sugar but these effects do not last long. We will monitor blood sugar during the infusions and make sure that participants blood sugar is ok before they leave.
Where is the study run from?
Imperial College Academic Health Science Centre, UK
When is the study starting and how long is it expected to run for?
May 2019 to February 2023
Who is funding the study?
1. National Institute for Health Research, UK
2. Medical Research Council, UK
3. NIHR Imperial Biomedical Research Centre, UK
4. Society for Endocrinology, UK
5. Imperial College London, UK
Who is the main contact?
Dr Chioma Izzi-Engbeyaa
c.izzi@imperial.ac.uk
Contact information
Public
Section of Endocrinology and Investigative Medicine
Imperial College London
6th Floor Commonwealth Building
Hammersmith Hospital Campus
Du Cane Road
London
W12 0NN
United Kingdom
 ORCID ID |
0000-0001-7599-0166 |
|---|---|
| Phone | +44 (0)20 3313 3242 |
| imperial.kisspeptin@nhs.net |
Scientific
Section of Endocrinology and Investigative Medicine
Imperial College London
6th Floor Commonwealth Building
Hammersmith Hospital Campus
Du Cane Road
London
W12 0NN
United Kingdom
| ORCID ID |
0000-0001-7599-0166 |
|---|---|
| Phone | +44 (0)20 3313 3242 |
| c.izzi@imperial.ac.uk |
Study information
| Study design | Single-blinded randomized two-way crossover study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised cross over trial |
| Study setting(s) | Other |
| Study type | Other |
| Participant information sheet | http://imperial.crf.nihr.ac.uk/studies/repromet/ |
| Scientific title | Physiological studies of hormones which control metabolism and reproduction |
| Study acronym | REPROMET |
| Study hypothesis | The study aims to answer the questions: Part A: Do gut hormones affect reproductive hormone secretion? Part B: Do reproductive hormones affect gut hormones, glucose, insulin, appetite, food intake and energy expenditure? |
| Ethics approval(s) | Approved 26/04/2016, West London & GTAC Research Ethics Committee (The Old Chapel, Royal Standard Place, Nottingham, NG1 6FS; +44 (0)207 104 8124; NRESCommittee.London-WestLondon@nhs.net), ref: 16/LO/0391 |
| Condition | Reproductive hormone effects |
| Intervention | Part A: Intravenous infusion of vehicle during one study visit and intravenous infusion of a gut hormone (i.e. glucagon, glucagon-like peptide-1, oxyntomodulin, peptide-YY or substance P) during a separate study visit. Infusion order will be randomly assigned Part B (participants will be involved in one or more of the following): 1: Intravenous infusion of vehicle during one study visit and intravenous infusion of a reproductive hormone (kisspeptin or neurokinin B) during a separate study visit. Infusion order will be randomly assigned. Oral glucose tolerance tests (OGTT) will be performed during both study visits 2: Intravenous infusion of vehicle during one study visit and intravenous infusion of a reproductive hormone (kisspeptin or neurokinin B) during a separate study visit. Infusion order will be randomly assigned. Intravenous glucose tolerance tests (IVGTT) will be performed during both study visits 3: Intravenous infusion of vehicle during one study visit and intravenous infusion of a reproductive hormone (kisspeptin or neurokinin B) during a separate study visit. Infusion order will be randomly assigned. Mixed meal tolerance tests (MMTT) will be performed during both study visits Randomisation: Part A – An online random number generator (www.random.org) will be used to generate numbers for each participant at the time of study entry. Participants with an even number will receive vehicle infusion first and glucagon-like peptide-1 (GLP-1) infusion second. Participants with an odd number will receive GLP-1 infusion first and vehicle infusion second. This process will be repeated for paired peptide-YY infusion and vehicle infusion visits; glucagon infusion and vehicle infusion visits; oxyntomodulin infusion and vehicle infusion visits; and substance P infusion and vehicle infusion visits. Part B – An online random number generator (www.random.org) will be used to generate numbers for each participant at the time of study entry. Participants with an odd number will receive kisspeptin infusion first and vehicle infusion second. Participants with an even number will receive vehicle infusion first and kisspeptin infusion second. This process will be repeated for paired neurokinin B infusion and vehicle infusion visits |
| Intervention type | Other |
| Primary outcome measure | Part A: 1. Luteinising hormone (LH) pulsatility, LH levels, follicle-stimulating hormone levels and testosterone levels in males measured using blood tests during the vehicle and hormone infusions 2. Oestrogen and progesterone levels in females measured blood tests during the vehicle and hormone infusions Part B: 1. OGTT/IVGTT/MMTT insulin and glucose levels measured using blood tests during vehicle and hormone infusions 2. OGTT/IVGTT/MMTT insulin secretion measured using blood tests during vehicle and hormone infusions 3. OGTT/IVGTT/MMTT insulin sensitivity and disposition indices measured using blood tests during vehicle and hormone infusions 4. MMTT food intake measured using scales during vehicle and hormone infusions 5. MMTT Energy expenditure measured using calorimetry and infrared thermography during vehicle and hormone infusions |
| Secondary outcome measures | Part B: Pre- and post-meal nausea, hunger and fullness ratings measured using visual analogue scales during hormone and vehicle infusions. |
| Overall study start date | 23/05/2016 |
| Overall study end date | 01/02/2023 |
Eligibility
| Participant type(s) | Mixed |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 60 Years |
| Sex | Both |
| Target number of participants | 200 |
| Total final enrolment | 78 |
| Participant inclusion criteria | 1. Aged 18 – 60 years 2. Male or female 3. Stable body weight for the preceding 3 months 4. 12-lead ECG with no clinically significant abnormalities as judged by the investigators 5. Full blood count, urea and electrolytes, thyroid function tests, liver function tests and glucose within 2 x the upper limit of normal 6. Conditions that predispose subfertility: BMI >25, Pre-diabetes, Type 2 diabetes |
| Participant exclusion criteria | 1. History of any medical, psychological or other condition, or use of any medications, including over-the-counter products, which, in the opinion of the investigators, would either interfere with the study or potentially cause harm to the volunteer 2. Pregnancy or breastfeeding 3. History of hypersensitivity to any of the components of the infusions 4. Treatment with an investigational drug within the preceding 2 months 5. Volunteers who have or intend to donate blood or blood products within three months before or following study completion 6. A history of alcoholism or substance abuse within the preceding 5 years 7. A history of major haematological, renal, thyroid or hepatic abnormalities or significant cardiovascular disease 8. A history of cancer 9. Volunteers with a medical or psychological condition that would impair their ability to participate reliably in the study or give informed consent 10. Smoker |
| Recruitment start date | 23/05/2019 |
| Recruitment end date | 01/02/2023 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
London
W6 8RF
United Kingdom
Sponsor information
University/education
Joint Research and Compliance Office
Imperial College London and Imperial College Healthcare NHS Trust
Norfolk Place
London
W2 1PG
England
United Kingdom
| Phone | +44 (0) 207 594 9459 |
|---|---|
| becky.ward@imperial.ac.uk | |
| Website | http://www3.imperial.ac.uk/clinicalresearchgovernanceoffice |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Government organisation / National government
- Alternative name(s)
- Medical Research Council (United Kingdom), UK Medical Research Council, MRC
- Location
- United Kingdom
Private sector organisation / Research institutes and centers
- Alternative name(s)
- NIHR Imperial BRC, Imperial Biomedical Research Centre, BRC
- Location
- United Kingdom
Private sector organisation / Other non-profit organizations
- Alternative name(s)
- SFE
- Location
- United Kingdom
Government organisation / Universities (academic only)
- Alternative name(s)
- Imperial College of Science, Technology and Medicine, Imperial College London, UK, Imperial College London, London, England, Imperial College London in United Kingdom, imperialcollege, ICL
- Location
- United Kingdom
No information available
Results and Publications
| Intention to publish date | 16/08/2018 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Results will be published and presented at conferences in phases following completion of each phase of the study. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available as this study is a physiological study. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | Effects of Peptide YY on the reproductive axis in healthy young men | 01/03/2020 | 03/12/2019 | Yes | No |
| Results article | Effects of kisspeptin on glucose-stimulated insulin secretion, metabolites, gut hormones, appetite and food intake in healthy men | 01/12/2018 | 03/12/2019 | Yes | No |
| Protocol file | version V2 | 18/03/2019 | 09/12/2019 | No | No |
| Results article | Effects of kisspeptin on food intake in women with overweight or obesity | 11/04/2023 | 17/04/2023 | Yes | No |
| HRA research summary | 28/06/2023 | No | No | ||
| Results article | Acute effects of glucagon on reproductive hormone secretion in healthy men | 01/06/2020 | 26/02/2024 | Yes | No |
| Results article | Effects of glucagon-like peptide-1 on the reproductive axis in healthy men | 01/04/2020 | 26/02/2024 | Yes | No |
Additional files
- ISRCTN10114288_Protocol V2 18Mar2019.pdf
- uploaded 09/12/2019
Editorial Notes
26/02/2024: Publication references and total final enrolment added. The overall study end date was changed from 28/02/2024 to 01/02/2023.
17/04/2023: The following changes have been made:
1. Publication reference added.
2. The overall trial end date has been changed from 31/12/2023 to 01/02/2023 and the plain English summary updated accordingly.
09/03/2021: Recruitment to this study is no longer paused.
17/04/2020: Due to current public health guidance, recruitment for this study has been paused.
09/12/2019: Uploaded protocol (not peer reviewed)
03/12/2019: Trial’s existence confirmed by West London & GTAC Research Ethics Committee
