Type 2 DiabetesPhase 2ADOPTIONNCT05216172
AZD1656 in Transplantation With Diabetes tO PromoTe Immune TOleraNce
A Phase 2 study testing AZD1656 in people with Type 2 Diabetes and Diabetes Mellitus, Type 2, run by Queen Mary University of London at 1 site in United Kingdom.
Trial summary
AZD1656 in Transplantation with Diabetes tO PromoTe Immune TOleraNce: a single site, placebo-controlled, double-blind randomised clinical trial of AZD1656 in renal transplant patients with Type 2 diabetes Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Type 2 Diabetes, Diabetes Mellitus, Type 2, Renal Transplant
- What is being tested?
- AZD1656
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 13 Dec 2019to 11 Sep 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Females or males aged 18 years and above
- Having undergone renal transplantation at the Royal London Hospital within the previous 24 hours
- A pre-transplant diagnosis of Type 2 diabetes
- Provision of written, informed consent prior to any study specific procedures
- In women of childbearing potential* documentation of a negative pregnancy test during admission for renal transplant.
- Women of childbearing potential are defined as women following menarche until becoming post-menopausal, unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A post-menopausal state is defined as the absence of menses for 12 months without an alternative medical cause.
Who cannot join
- Unable to consent
- Known allergy/intolerance to AZD1656
- Pregnant or breastfeeding women
- Planning on becoming pregnant/unwilling to use highly effective contraception* during the 3 month treatment period and for 2 weeks afterwards (i) In the case of men with sexual partners who are women of childbearing potential: refusal to wear a condom and female partner planning on becoming pregnant/unwilling to use highly effective contraception* during the 3 month treatment period and for 2 weeks afterwards
- Clinically significant history of abnormal physical and/or mental health as judged by the investigator other than conditions related to chronic kidney disease
- Current or planned use of strong inhibitors of CYP2C8
Show all 13Show fewer
- Participation in an investigational drug trial in the 3 months prior to administration of the initial dose of study drug
- Highly effective contraception methods are defined as those that can achieve a failure rate of <1% per year when used correctly and consistently. These include:
- Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation - either oral, transvaginal or transdermal
- Progestogen-only hormonal contraception associated with inhibition of ovulation - either oral, injectable or implantable
- Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS)
- Bilateral tubal occlusion
- Vasectomised partner - provided that the partner is the sole sexual partner of the participant and that the vasectomised partner has received medical assessment of surgical success
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Royal London Hospital Barts Health NHS Trust
London, E1 1BB
About this study
AZD1656 in Transplantation with Diabetes tO PromoTe Immune TOleraNce: a single site, placebo-controlled, double-blind randomised clinical trial of AZD1656 in renal transplant patients with Type 2 diabetes
Read the detailed description
Transplant recipients with pre-existing Type 2 diabetes frequently experience a deterioration in glycaemic control in the early post-transplant period, largely due to the significant immunosuppression burden at this stage. Elevated glucose profiles have been associated with poorer graft outcomes. The glucokinase activator AZD1656 has been shown to be a potent anti diabetic medication and safe in patients with T2DM, including those with chronic kidney disease. Recent data has shown that glucokinase activation increases regulatory T cell (Treg) migration and trafficking. The investigators propose to study the safety and efficacy of AZD1656 in optimising the glycaemic control and in stimulating Treg migration to the transplant kidney in a population of renal transplant patients with pre-existing T2DM.
ADOPTION is a single site, placebo-controlled, double-blind randomised clinical trial of AZD1656 in patients with Type 2 diabetes who have received a new renal transplant. Eligible, consented patients are randomised to a 3 month course of either active drug or placebo within 24 hours of transplantation. Clinical and laboratory data will be collected and assessed at baseline and throughout their participation in the study. The study plans to enrol 50 patients. There are no interim analyses planned. The primary endpoint will be the mean change in peripheral Tregs between baseline and 3 months as analysed by flow cytometry.
Ethical approval was obtained from the East of England - Cambridge East Ethics Committee (REC 19/EE/0209) prior to commencing the study. All study-related data will be used by the Sponsor in accordance with local data protection law. Results of the trial will be submitted for publication in a peer-reviewed journal.
- Conditions
- Type 2 Diabetes, Diabetes Mellitus, Type 2, Renal Transplant, Kidney Transplant; Complications, End Stage Renal Disease
- Being tested
- AZD1656, Placebo
- Keywords
- Type 2 Diabetes Mellitus, Diabetes Mellitus, Renal transplantation, Regulatory T cells, AZD1656
- Medical subject headings
- Diabetes Mellitus, Type 2, Kidney Failure, Chronic, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD1656Drug
active drug
PlaceboDrug
placebo
| Study group | Role | What they receive |
|---|---|---|
| AZD1656 | Experimental | AZD1656 100mg BD for 3 months Receives: Drug: AZD1656 |
| placebo | Placebo comparator | placebo 100mg BD for 3 months Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
peripheral regulatory T cells
Change in mean peripheral Treg cell number between baseline and 3 months measured using flow cytometry analysis (FACS) in AZD1656 and placebo arms
Measured: 14 weeks
Secondary outcomes (9)
regulatory T cells in renal transplant
Histological staining for Treg cells in renal biopsy tissue between baseline and 3 month protocol biopsy
Measured: 3 months
delayed graft function
Incidence of delayed graft function, defined as the need for dialysis within 1 week post-transplant
Measured: 1 week
glycemic control: HbA1c
Diabetic control between baseline and month 3 using change in HbA1c measurement
Measured: 3 months
number of participants with increase or decrease in concurrent anti-diabetic medication
Dose of other anti-diabetic medication between baseline and month 3 (descriptive)
Measured: 3 months
incidence of treatment emergent adverse events
safety endpoints including hypoglycaemic episodes
Measured: 3 months
change in HOMA-IR measurement between baseline and month 3
Insulin resistance: HOMA IR measurement at month 3
Measured: 3 months
kidney transplant function
Graft function: (eGFR) at month 3
Measured: 3 months
kidney transplant rejection
Episodes of acute rejection (defined as biopsy proven acute rejection)
Measured: 3 months
incidence of treatment emergent adverse events (with particular reference to episodes of infection)
Episodes of opportunistic infections: bacterial and viral (descriptive)
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2022
- Study start13 Dec 2019
- Primary completion11 Sep 2022
- Study completion11 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- More trials run by Queen Mary University of LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Single site, placebo controlled, double blind randomised clinical trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Queen Mary University of London
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Kieran McCafferty, M.B., B.Chir, Principal investigator, Barts Health NHS Trust; Queen Mary University London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05216172
- Sponsor's protocol ID
- 252155
- Acronym
- ADOPTION
- Status last verified
- Jun 2024
- First submitted
- 17 Jan 2022
- Last updated
- 20 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in any published article, after de-identification (text, tables, figures, and appendices)
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- AZD1656 in Transplantation With Diabetes tO PromoTe Immune TOleraNce
- ClinicalTrials.gov ID
- NCT05216172
- Acronym / sponsor ID
- ADOPTION / 252155
- Conditions
- Type 2 Diabetes, Diabetes Mellitus, Type 2, Renal Transplant, Kidney Transplant; Complications, End Stage Renal Disease
- Keywords
- Type 2 Diabetes Mellitus, Diabetes Mellitus, Renal transplantation, Regulatory T cells, AZD1656
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Queen Mary University of LondonUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- 13 Dec 2019 (actual)
- Primary completion
- 11 Sep 2022 (actual)
- Study completion
- 11 Sep 2022 (actual)
- First posted
- 31 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
AZD1656 in Transplantation with Diabetes tO PromoTe Immune TOleraNce: a single site, placebo-controlled, double-blind randomised clinical trial of AZD1656 in renal transplant patients with Type 2 diabetes
Detailed description
Transplant recipients with pre-existing Type 2 diabetes frequently experience a deterioration in glycaemic control in the early post-transplant period, largely due to the significant immunosuppression burden at this stage. Elevated glucose profiles have been associated with poorer graft outcomes. The glucokinase activator AZD1656 has been shown to be a potent anti diabetic medication and safe in patients with T2DM, including those with chronic kidney disease. Recent data has shown that glucokinase activation increases regulatory T cell (Treg) migration and trafficking. The investigators propose to study the safety and efficacy of AZD1656 in optimising the glycaemic control and in stimulating Treg migration to the transplant kidney in a population of renal transplant patients with pre-existing T2DM.
ADOPTION is a single site, placebo-controlled, double-blind randomised clinical trial of AZD1656 in patients with Type 2 diabetes who have received a new renal transplant. Eligible, consented patients are randomised to a 3 month course of either active drug or placebo within 24 hours of transplantation. Clinical and laboratory data will be collected and assessed at baseline and throughout their participation in the study. The study plans to enrol 50 patients. There are no interim analyses planned. The primary endpoint will be the mean change in peripheral Tregs between baseline and 3 months as analysed by flow cytometry.
Ethical approval was obtained from the East of England - Cambridge East Ethics Committee (REC 19/EE/0209) prior to commencing the study. All study-related data will be used by the Sponsor in accordance with local data protection law. Results of the trial will be submitted for publication in a peer-reviewed journal.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Single site, placebo controlled, double blind randomised clinical trial
| Arm | Type | Receives |
|---|---|---|
| AZD1656 | Experimental | Drug: AZD1656AZD1656 100mg BD for 3 months |
| placebo | Placebo comparator | Drug: Placeboplacebo 100mg BD for 3 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Females or males aged 18 years and above
- Having undergone renal transplantation at the Royal London Hospital within the previous 24 hours
- A pre-transplant diagnosis of Type 2 diabetes
- Provision of written, informed consent prior to any study specific procedures
- In women of childbearing potential* documentation of a negative pregnancy test during admission for renal transplant.
Key exclusion criteria (13 listed)
- Unable to consent
- Known allergy/intolerance to AZD1656
- Pregnant or breastfeeding women
- Planning on becoming pregnant/unwilling to use highly effective contraception* during the 3 month treatment period and for 2 weeks afterwards (i) In the case of men with sexual partners who are women of childbearing potential: refusal to wear a condom and female partner planning on becoming pregnant/unwilling to use highly effective contraception* during the 3 month treatment period and for 2 weeks afterwards
- Clinically significant history of abnormal physical and/or mental health as judged by the investigator other than conditions related to chronic kidney disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD1656active drug | Drug | AZD1656 |
| Placeboplacebo | Drug | placebo |
Primary outcome
peripheral regulatory T cells
Time frame: 14 weeks
Change in mean peripheral Treg cell number between baseline and 3 months measured using flow cytometry analysis (FACS) in AZD1656 and placebo arms
9 secondary outcomes
regulatory T cells in renal transplant
Time frame: 3 months
delayed graft function
Time frame: 1 week
glycemic control: HbA1c
Time frame: 3 months
number of participants with increase or decrease in concurrent anti-diabetic medication
Time frame: 3 months
incidence of treatment emergent adverse events
Time frame: 3 months
change in HOMA-IR measurement between baseline and month 3
Time frame: 3 months
kidney transplant function
Time frame: 3 months
kidney transplant rejection
Time frame: 3 months
incidence of treatment emergent adverse events (with particular reference to episodes of infection)
Time frame: 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2024.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in any published article, after de-identification (text, tables, figures, and appendices)
Related trials for Type 2 Diabetes
Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kieran McCafferty, M.B., B.Chir principal investigator
Barts Health NHS Trust; Queen Mary University London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AZD1656 in people with Type 2 Diabetes and Diabetes Mellitus, Type 2, run by Queen Mary University of London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
peripheral regulatory T cells (time frame: 14 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jun 2024.