Can a dietary supplement providing natural cGP (cyclic Glycine-Proline) compliment the body’s own internal levels of cGP and help improve the metabolic health of type 2 diabetes sufferers and aid in the recovery of complications associated with metabolic syndrome
| ISRCTN | ISRCTN84351085 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN84351085 |
| EudraCT/CTIS number | Nil Known |
| Secondary identifying numbers | MR-42-23-028752 |
- Submission date
- 25/07/2024
- Registration date
- 29/07/2024
- Last edited
- 30/07/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English Summary
Background and study aims
Metabolic syndrome is a cluster of clinical manifestations including type-2 diabetes mellitus (T2DM), hypertension and dyslipidemia. Elevated blood glucose and insulin levels damage capillary networks and cause diabetic peripheral neuropathy, hypertension and other complications due to loss of microcirculation. With no cure, the prognosis of peripheral neuropathy is poor and a major cause of limb amputation. The 5-year survival rate after limb amputation is about 2 years, shorter than colon, breast and prostate cancers. Cyclic glycine-proline (cGP) is a trophic molecule that keeps the function of insulin-like growth factor-1 (IGF-1) normal. The key function of IGF-1 is to maintain the network of small blood vessels and capillaries. Thus, we hypothesize that the administration of natural cGP, via an orally bioavailable dietary supplement, may improve foot sensation, blood pressure and glucose metabolism by supporting a healthy microcirculation.
Who can participate?
Male and females aged between 45 and 80 years with medical histories of T2DM, hypertension and foot peripheral neuropathy can volunteer to participate in the trial.
What does the study involve?
One group will take one capsule/day providing 20 - 25µg natural cGP (low dose) and the other group taking one capsule/day delivering 40 - 45µg natural cGP (high dose). The capsules are formulated using natural food ingredients sourced from New Zealand and encapsulated in a GMP facility. Three hospital visits are planned over a 6-month trial period. At each hospital visit foot sensation is to be assessed using Semmes-Weinstein monofilament, vibration and warm/cold perception threshold tests. These tests are the routine practice for assessing feet' sensory function. Fasting blood samples (10ml) are to be collected, and blood pressure is measured during each hospital visit. Participants are instructed to remain on their medications for hypertension, hyperlipidemia, and diabetes and to maintain their current lifestyle throughout the trial.
What are the possible benefits and risks of participating?
Our body naturally produces cGP keeping the function of IGF-1 normal. When our own cGP production is insufficient we experience metabolic dysfunction. Oral supplementation with a physiological dose of natural cGP designed to top up the shortage of our own cGP would be beneficial and have minimal interaction with the medications that the participants are using.
Where is the study run from?
This study will be conducted at the Department of Endocrinology, Tianyou Hospital, Wuhan University of Science and Technology, China.
When is the study starting and how long is it expected to run for?
May 2020 to May 2023
Who is funding the study?
The study is co-funded by The Health Commission, Hubei, China, and The cGP Lab Ltd., New Zealand.
Who is the main contact?
Dr J Guan, Jian.guan@thecgplab.com
Contact information
Public, Scientific, Principal Investigator
300 Richmond Road, Grey Lynn
Auckland
1021
New Zealand
 ORCID ID |
0000-0002-2847-1627 |
|---|---|
| Phone | +64 0210366863 |
| jian.guan@thecgplab.com |
Study information
| Study design | Two-armed open-label study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Prevention, Treatment, Efficacy |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet. |
| Scientific title | An observational study suggested a cause-effect relationship between plasma cGP and clinical manifestations of Type 2 diabetes mellitus (T2DM) and its associated vascular complications. To confirm such relationship, this open label trial is designed to examine the efficacy of natural cGP supplementation on manifestations of T2DM. |
| Study hypothesis | As a natural reaction, endogenous cGP (cyclic glycine-proline) increases, however, the response is insufficient to address metabolic disorders and vascular complications. This leads us to hypothesise that further increasing plasma cGP via oral administration of natural cGP may improve clinical outcomes of metabolic syndrome. |
| Ethics approval(s) |
Approved 01/05/2020, The Ethics Committee of Tianyou Hospital, Affiliated to Wuhan University of Science & Technology (Tianyou Hospital, 9 Tujialing, Wuchang, Wuhan, 430064, China; +8613554623321; yangyang1003@wust.edu.cn), ref: Approval number: 2021-02-28; Revised approval number LL2024-02-08-01 |
| Condition | The efficacy of cGP in vascular complications in patients with diabetes |
| Intervention | To confirm the cause-effect relationship of cyclic glycine-proline (cGP) to manifestations of type 2 diabetes (T2DM), an open-label study is used to examine the efficacy of natural cGP supplementation on manifestations of T2DM. The two-armed open-label trial is to be conducted at the Tianyou Hospital, Wuhan University of Science and Technology, China. Thirty-eight T2DM participants with foot sensory deficits will be allocated into 2 cohorts and receive either 20 - 25µg or 40 - 45µg natural cGP daily. There will be three hospital visits during a 6-month trial. Foot sensation is to be assessed using Semmes-Weinstein monofilament, vibration and warm/cold perception threshold tests. Blood pressure measured. Fasting blood samples will be collected. |
| Intervention type | Supplement |
| Primary outcome measure | Foot sensation measured using Semmes-Weinstein monofilament, vibration and warm/cold perception threshold tests at three hospital visits (Before supplementation, after 3 months of supplementation, and after 6 months of supplementation) |
| Secondary outcome measures | Measured before supplementation, after 3 months of supplementation, and after 6 months of supplementation: 1. Systolic and diastolic blood pressure measured using a sphygmomanometer at three hospital visits 2. Glucose intolerance measured using fasting blood glucose, HBA1c (%), and triglyceride/glucose index at three hospital visits |
| Overall study start date | 01/05/2020 |
| Overall study end date | 01/05/2023 |
Eligibility
| Participant type(s) | Healthy volunteer, Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 45 Years |
| Upper age limit | 80 Years |
| Sex | Both |
| Target number of participants | 40 |
| Total final enrolment | 38 |
| Participant inclusion criteria | 1. Male and female participants aged between 45 and 80 years old 2. More than 8 years of medical history of Type 2 Diabetes Mellitus (T2DM) 3. Current diagnosis of foot diabetic peripheral neuropathy (DPN) 4. Diagnosis of T2DM based on: 4.1. Fasting glucose ≥ 7 mmol/L and/or 4.2. HbA1c ≥ 6.5% 5. Diagnosis of foot DPN based on: 5.1. Self-reporting symptoms 5.2. Foot sensory testing scores 6. Inclusion criteria are independent of: 6.1. Body Mass Index (BMI) 6.2. Blood pressure 6.3. Plasma lipid profiles 6.4. Other complications of T2DM |
| Participant exclusion criteria | 1. Type 1 diabetes 2. Diabetic foot ulcers 3. Any other cause of peripheral neuropathy (drug or injury or Covid-19 associated peripheral neuropathy) 4. Medical history of degenerative neurological conditions 5. History of cognitive impairment 6. Major mental health issues such as: 6.1. Schizophrenia 6.2. Severe depression 6.3. Anxiety |
| Recruitment start date | 01/05/2021 |
| Recruitment end date | 01/05/2023 |
Locations
Countries of recruitment
- China
Study participating centre
Wuhan
430064
China
Sponsor information
Industry
300 Richmond Road, Grey Lynn
Auckland
1021
New Zealand
| Phone | +64 21986022 |
|---|---|
| amanda.wiggins@thecgplab.com | |
| Website | https://cgpmax.com/ |
University/education
Tianyou Hospital
Wuhan
43008
China
| Phone | +64 13554623321 |
|---|---|
| yangyang1003@wust.edu.cn | |
| Website | http://www.wust.edu.cn/default.html |
"ROR" |
https://ror.org/00e4hrk88 |
Funders
Funder type
Industry
No information available
Government organisation / Local government
- Alternative name(s)
- Hubei Provincial Health Commission, 湖北省卫生健康委员会
- Location
- China
Results and Publications
| Intention to publish date | 01/05/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request, Published as a supplement to the results publication |
| Publication and dissemination plan | Planned publication in a peer-reviewed journal |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be available upon request from Jian Guan, jian.guan@thecgplab.com The datasets generated and/or analysed during the current study will be published as a supplement to the results publication • The type of data that will be shared Raw data that collected during the trial without any personal information of participants. • Timing for availability After the main data being published. • Whether consent from participants was required and obtained Yes • Comments on data anonymization The data will be shared without private information being divulged. The individual participant data were collected and recorded in Chinese. |
Editorial Notes
30/07/2024: Internal review.
29/07/2024: Trial's existence confirmed by Tianyou Hospital.
