Type 2 DiabetesNCT06533007
PDE3B in Metabolic Regulation
An observational study of Type 2 Diabetes and Cardiometabolic Syndrome, run by Cambridge University Hospitals NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Phosphodiesterase 3B (PDE3B), an enzyme responsible for the degradation of cyclic AMP and GMP (two important second messengers used for intracellular signal transduction), has been associated with cardiometabolic outcomes. Read more about this study
- Who is it for?
- Ages 21 to 75 years
- Conditions the study is for
- Type 2 Diabetes, Cardiometabolic Syndrome, Cardiovascular Diseases
- How many people
- 40 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Sep 2025to Sep 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 21 to 75 years
- All sexes
- Adult, Older adult
Study population: Participants with heterozygous for PDE3B LoF variants will be recruited from existing research cohorts (i.e., the Oxford Biobank, the NIHR BioResource at the University of Cambridge and the Fenland study populations (1:700 frequency of the LoF variant). Subsequently, individuals without the variant of interest will be recruited from the same cohorts to establish a WT group of individuals matched for age, sex, race/ethnicity, and body fat percent.
Who may be able to join
- willing and able to give informed consent for participation in the study
- aged 21-75 years
- men and women
Who cannot join
- unstable weight (>5% change the last 2 months)
- type 2 diabetes or other major organ dysfunction
- cancer in last 5 years
- gastrointestinal or bariatric surgery (except cholecystectomy and appendectomy)
- conditions that render subject unable to complete all testing procedures (including individuals with known allergies or contraindications to the medications used in this study)
- use of medications that affect the study outcome measures or increase the risk of study procedures and that cannot be temporarily discontinued
Show all 10Show fewer
- smoking
- illegal drug use
- pregnant or lactating
- unable to grant voluntary informed consent or comply with the study instructions
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: The Role of Phosphodiesterase 3B in the Regulation of Human Adipose Tissue Biology and Systemic Glucose and Lipid Homeostasis
Phosphodiesterase 3B (PDE3B), an enzyme responsible for the degradation of cyclic AMP and GMP (two important second messengers used for intracellular signal transduction), has been associated with cardiometabolic outcomes. Results from animal studies indicate that abolishing PDE3B function may be associated with unfavourable metabolic profile; however, preliminary human studies suggest that heterozygous loss of function (LoF) variants in the PDE3B gene have been associated with cardiometabolic improvements. Therefore, the effect of PDE3B on human adipose tissue metabolic pathways remains poorly understood.
Accordingly, the investigators propose to conduct a recall-by-genotype, case-control study in a group of people with LoF variants in the PDE3B gene and a matched group without the variant (wild type, WT) to determine differences on key metabolic features: 1) adipose tissue biology (i.e., mitochondrial function, adipocyte morphology, gene expression and in vivo lipolysis in the basal and/or the insulin-stimulated state); 2) systemic lipid and glucose metabolism using the hyperinsulinemic-euglycemic clamp procedure.
The proposed investigations will elucidate the role of PDE3B on adipose tissue and systemic glucose and lipid metabolism in humans and whether modulating PDE3B activity constitutes a target for the prevention and treatment of cardiometabolic disease.
Read the detailed description
Phosphodiesterase 3B (PDE3B) is a protein that plays a role in how cells handle nutrients (i.e. glucose and fats). The investigators have recently found that people who have a gene variant (i.e., change in the DNA) that reduces the function of the PDE3B protein may be protected from the development of diabetes and heart disease. However, it is unclear how this happens.
The aims of this study are to examine:
- What is the role of PDE3B in fat tissue function?
- How does PDE3B influence the way one's body handles blood sugars and lipids?
To this end, the investigators propose to study people who have a variant that reduces the function of that PDE3B and an equal number of people with the typical genotype.
Participants will be asked to attend two visits:
- a 4-h screening visit: involving a medical examination, blood tests before/after drinking a sugary drink and assessment of lifestyle (physical activity/sleep/diet) using questionnaires and smartwatch.
- a 24-h metabolic testing visit (only for eligible participants): involving an infusion of insulin and collection of blood samples and fat tissue from the lower tummy.
These investigations will provide a great opportunity to study how people with or without the variant handle fat, sugars and lipids in their bodies. They will also help the scientific community to understand the role of PDE3B in humans and possibly develop new ways to prevent or fight conditions like diabetes and heart disease.
- Medical subject headings
- Diabetes Mellitus, Type 2, Metabolic Syndrome, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| PDE3B LoF group | Individuals heterozygous for a loss-of-function variant in the PDE3B gene | |
| Wild type group | Individuals who do not carry the loss-of-function variant for PDE3B gene but otherwise matched for age, sex, race/ethnicity, and body fat percent. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lipolysis
Lipolysis will be assessed as the palmitate rate of appearance by using infusion of stable isotope tracers.
Measured: baseline
Secondary outcomes (3)
Adipose tissue gene expression
Changes in the expression of genes will be assessed by using RNA sequencing
Measured: baseline
Insulin sensitivity
Insulin sensitivity will be assessed by using a hyperinsulinemic euglycemic clamp procedure in conjunction with infusion of stable isotope tracers.
Measured: baseline
Insulin secretion
Insulin sensitivity will be assessed by using an oral glucose tolerance test
Measured: baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2024
- Study start1 Sep 2025
- Primary completionSep 2028 (estimated)
- Study completionSep 2029 (estimated)
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.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cambridge University Hospitals NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University of Cambridge
- Responsible party
- Principal investigator, Maria Chondronikola, Cambridge University Hospitals NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06533007
- Sponsor's protocol ID
- 343566
- Status last verified
- Nov 2025
- First submitted
- 17 Jul 2024
- Last updated
- 24 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Phosphodiesterase 3B in the Regulation of Human Adipose Tissue Biology and Systemic Glucose and Lipid Homeostasis
- ClinicalTrials.gov ID
- NCT06533007
- Acronym / sponsor ID
- 343566
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Cambridge University Hospitals NHS Foundation TrustUniversity, hospital or other
- Collaborators
- University of Cambridge
- Study start
- 1 Sep 2025 (actual)
- Primary completion
- Sep 2028 (estimated)
- Study completion
- Sep 2029 (estimated)
- First posted
- 1 Aug 2024 (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.
Phosphodiesterase 3B (PDE3B), an enzyme responsible for the degradation of cyclic AMP and GMP (two important second messengers used for intracellular signal transduction), has been associated with cardiometabolic outcomes. Results from animal studies indicate that abolishing PDE3B function may be associated with unfavourable metabolic profile; however, preliminary human studies suggest that heterozygous loss of function (LoF) variants in the PDE3B gene have been associated with cardiometabolic improvements. Therefore, the effect of PDE3B on human adipose tissue metabolic pathways remains poorly understood.
Accordingly, the investigators propose to conduct a recall-by-genotype, case-control study in a group of people with LoF variants in the PDE3B gene and a matched group without the variant (wild type, WT) to determine differences on key metabolic features: 1) adipose tissue biology (i.e., mitochondrial function, adipocyte morphology, gene expression and in vivo lipolysis in the basal and/or the insulin-stimulated state); 2) systemic lipid and glucose metabolism using the hyperinsulinemic-euglycemic clamp procedure.
The proposed investigations will elucidate the role of PDE3B on adipose tissue and systemic glucose and lipid metabolism in humans and whether modulating PDE3B activity constitutes a target for the prevention and treatment of cardiometabolic disease.
Detailed description
Phosphodiesterase 3B (PDE3B) is a protein that plays a role in how cells handle nutrients (i.e. glucose and fats). The investigators have recently found that people who have a gene variant (i.e., change in the DNA) that reduces the function of the PDE3B protein may be protected from the development of diabetes and heart disease. However, it is unclear how this happens.
The aims of this study are to examine:
- What is the role of PDE3B in fat tissue function?
- How does PDE3B influence the way one's body handles blood sugars and lipids?
To this end, the investigators propose to study people who have a variant that reduces the function of that PDE3B and an equal number of people with the typical genotype.
Participants will be asked to attend two visits:
- a 4-h screening visit: involving a medical examination, blood tests before/after drinking a sugary drink and assessment of lifestyle (physical activity/sleep/diet) using questionnaires and smartwatch.
- a 24-h metabolic testing visit (only for eligible participants): involving an infusion of insulin and collection of blood samples and fat tissue from the lower tummy.
These investigations will provide a great opportunity to study how people with or without the variant handle fat, sugars and lipids in their bodies. They will also help the scientific community to understand the role of PDE3B in humans and possibly develop new ways to prevent or fight conditions like diabetes and heart disease.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PDE3B LoF group | – | –Individuals heterozygous for a loss-of-function variant in the PDE3B gene |
| Wild type group | – | –Individuals who do not carry the loss-of-function variant for PDE3B gene but otherwise matched for age, sex, race/ethnicity, and body fat percent. |
Who may qualify
- Ages
- 21 to 75 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Participants with heterozygous for PDE3B LoF variants will be recruited from existing research cohorts (i.e., the Oxford Biobank, the NIHR BioResource at the University of Cambridge and the Fenland study populations (1:700 frequency of the LoF variant). Subsequently, individuals without the variant of interest will be recruited from the same cohorts to establish a WT group of individuals matched for age, sex, race/ethnicity, and body fat percent.
Key inclusion criteria (3 listed)
- willing and able to give informed consent for participation in the study
- aged 21-75 years
- men and women
Key exclusion criteria (10 listed)
- unstable weight (>5% change the last 2 months)
- type 2 diabetes or other major organ dysfunction
- cancer in last 5 years
- gastrointestinal or bariatric surgery (except cholecystectomy and appendectomy)
- conditions that render subject unable to complete all testing procedures (including individuals with known allergies or contraindications to the medications used in this study)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Lipolysis
Time frame: baseline
Lipolysis will be assessed as the palmitate rate of appearance by using infusion of stable isotope tracers.
3 secondary outcomes
Adipose tissue gene expression
Time frame: baseline
Insulin sensitivity
Time frame: baseline
Insulin secretion
Time frame: baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2025.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Type 2 Diabetes and Cardiometabolic Syndrome, run by Cambridge University Hospitals NHS Foundation Trust 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 3 inclusion and 10 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: enrolling by invitation, as of the sponsor's last update on 24 Nov 2025. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Lipolysis (time frame: baseline). 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 24 Nov 2025.