Diabetes Mellitus, Type 2Phase 3NCT06203275
The G Protein-Coupled Receptor Kinase Type 2 Inhibitor Paroxetine as Adjunctive Therapy to Improve Insulin Sensitivity in Patients With Type 2 Diabetes Mellitus
A Phase 3 study testing Paroxetine in people with Diabetes Mellitus, Type 2, run by aya ramadan ashmawy sarhan.
Trial summary
The aim of this study is to investigate the effect of GRK2 inhibitor paroxetine on insulin resistance in patients with type 2 diabetes mellitus. Read more about this study
- Who is it for?
- Ages 20 to 65 years
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- Paroxetine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- No sites listed yet
- Study dates
- Jan 2024to Jan 2026
- Phase
- Phase 3
- 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 20 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with established diagnosis of type 2 diabetes.
- Patients with type 2 diabetes treated with metformin based combined oral hypoglycemic ( metformin plus DDP4 inhibitor or metformin plus sulfonylureas or metformin plus GLP-1 analogues)
- Glycated hemoglobin (HbA1c) ≥ 7% and ≤9
- Age between 20 and 65 years
- BMI ≥25 kg/m2
Who cannot join
- Pregnant and lactating women
- Patients with diabetes complications except for hyperlipidemia if any.
- Patients with acute or chronic illness (such as flu, cancer, rheumatoid arthritis, etc….)
- Patients with renal impairment (S.Cr > 1.5 mg/dl) and hepatic impairment (Bilirubin level > 1.2 mg/dl).
- Patients with cardiovascular diseases
- Patients with condition that predispose to acidosis as COPD
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- Patients with glaucoma
- Patients with thyroid disorders
- Patients on the medications that affect carbohydrate metabolism such as beta blockers, contraceptives, thiazide diuretic, corticosteroids, sympathomimetic
- Patients treated with any oral anti-diabetes agents other oral hypoglycemic agents or treated with insulin
- Patients stabilized anticoagulants, antiplatelet, antipsychotics, MAOIs, amphetamines, NSAIDs, corticosteroids, ergotamine, levothyroxine, narcotic analgesic, tramadol, liver microsomal enzyme inhibitors and liver microsomal enzyme inducers
About this study
The aim of this study is to investigate the effect of GRK2 inhibitor paroxetine on insulin resistance in patients with type 2 diabetes mellitus.
Read the detailed description
Type 2 Diabetes Mellitus (T2DM) is one of the most common metabolic disorders worldwide and its development is primarily caused by a combination of two main factors including defective insulin secretion by pancreatic β-cells and the inability of insulin sensitive tissues to respond to insulin.
Type 2 Diabetes Mellitus (T2DM) shares an intimate relationship with altered metabolism through the development of insulin resistance )IR(.
The G protein-coupled receptor kinase type 2 (GRK2) is involved in the regulation of many pivotal cell functions and is a key player in human health and diseases.In fact, GRK2 regulates insulin signaling through serine phosphorylated events. G protein-coupled receptor kinase type 2 up-regulation inhibits insulin signaling and glucose extraction due to a time dependent insulin-stimulated association of GRK2 with Insulin Receptor Substrate 1 (IRS1), leading to IRS1 serine phosphorylation and inactivation. Inhibition of hepatic GRK2 expression is sufficient to improve glucose homeostasis and insulin sensitivity, which eventually improves endothelial dysfunction in T2DM.
Preclinical studies reported that, genetic ablation of GRK2 in mice reduced insulin resistance. In this sense, inhibition of GRK2 activity could improve insulin sensitivity and might provide a new therapeutic target for the treatment of IR and T2DM. Paroxetine, an FDA-approved selective serotonin reuptake inhibitor (SSRI), was identified as a potent GRK2 inhibitor with higher selectivity for GRK2 over other GRKs both in vivo and in vitro.
Paroxetine binds to the active site of GRK2 and stabilizes the kinase domain in a conformation that inhibits G protein-coupled receptor (GPCR) phosphorylation and desensitization.6 A case report study demonstrated that during 3 months of paroxetine treatment, 35-year-old woman with poorly controlled T2DM experienced an increased frequency of hypoglycemic episodes. After discontinuation of paroxetine, her awareness of hypoglycemia was dramatically improved. The authors hypothesized that her hypoglycemic unawareness might be caused by autonomic dysfunction, which is an atypical manifestation of serotonin syndrome. Paroxetine also increased insulin sensitivity in non-diabetic patients who experienced remitted depression in a randomized trial.
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- Paroxetine, Placebo
- Keywords
- GRK2 inhibitor, insulin resistance, diabetes, paroxetine
- Medical subject headings
- Diabetes Mellitus, Type 2, Insulin Resistance, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ParoxetineDrug
intervention group n=22 Patients with type 2 diabetes treated with metformin based combined oral hypoglycemic ( metformin plus DDP4 inhibitor or metformin plus sulfonylureas or metformin plus GLP-1 analogues) plus paroxetine 12.5 mg daily
PlaceboDrug
Patients with type 2 diabetes treated with metformin based combined oral hypoglycemic ( metformin plus DDP4 inhibitor or metformin plus sulfonylureas or metformin plus GLP-1 analogues) plus placebo daily
| Study group | Role | What they receive |
|---|---|---|
| group 1 (control group) | Placebo comparator | which will receive metformin based combined oral hypoglycemic plus placebo tablets Receives: Drug: Placebo |
| group II (intervention group) | Active comparator | which will receive metformin based combined oral hypoglycemic plus 12.5 mg paroxetine daily at morning. Receives: Drug: Paroxetine |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome is the change in glycated Hemoglobin (HbA1c).
Measured: 3 months
Change in HOMA-IR .
Measured: 3 months
Secondary outcomes (1)
The secondary outcome is the change in expression of GRK2
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 posted12 Jan 2024
- Study startJan 2024 (estimated)
- Primary completionJan 2025 (estimated)
- Study completionJan 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes Mellitus, Type 2Studies 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
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This proof of concept pilot study is designed as a randomized placebo controlled parallel trial. Forty four patients of both gender with confirmed diagnosis of T2DM will be randomized using sealed envelope method into two groups
- Masking
- None (open label)
- Enrolment
- 44 participants (estimated)
Sponsor and investigators
- Lead sponsor
- aya ramadan ashmawy sarhan
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, aya ramadan ashmawy sarhan, Tanta University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06203275
- Sponsor's protocol ID
- paroxetine in type 2 diabetes
- Status last verified
- Nov 2023
- First submitted
- 17 Nov 2023
- Last updated
- 12 Jan 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The G Protein-Coupled Receptor Kinase Type 2 Inhibitor Paroxetine as Adjunctive Therapy to Improve Insulin Sensitivity in Patients With Type 2 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT06203275
- Acronym / sponsor ID
- paroxetine in type 2 diabetes
- Conditions
- Diabetes Mellitus, Type 2
- Keywords
- GRK2 inhibitor, insulin resistance, diabetes, paroxetine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 44 participants (estimated)
- Lead sponsor
- aya ramadan ashmawy sarhanUniversity, hospital or other
- Study start
- Jan 2024 (estimated)
- Primary completion
- Jan 2025 (estimated)
- Study completion
- Jan 2026 (estimated)
- First posted
- 12 Jan 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.
The aim of this study is to investigate the effect of GRK2 inhibitor paroxetine on insulin resistance in patients with type 2 diabetes mellitus.
Detailed description
Type 2 Diabetes Mellitus (T2DM) is one of the most common metabolic disorders worldwide and its development is primarily caused by a combination of two main factors including defective insulin secretion by pancreatic β-cells and the inability of insulin sensitive tissues to respond to insulin.
Type 2 Diabetes Mellitus (T2DM) shares an intimate relationship with altered metabolism through the development of insulin resistance )IR(.
The G protein-coupled receptor kinase type 2 (GRK2) is involved in the regulation of many pivotal cell functions and is a key player in human health and diseases.In fact, GRK2 regulates insulin signaling through serine phosphorylated events. G protein-coupled receptor kinase type 2 up-regulation inhibits insulin signaling and glucose extraction due to a time dependent insulin-stimulated association of GRK2 with Insulin Receptor Substrate 1 (IRS1), leading to IRS1 serine phosphorylation and inactivation. Inhibition of hepatic GRK2 expression is sufficient to improve glucose homeostasis and insulin sensitivity, which eventually improves endothelial dysfunction in T2DM.
Preclinical studies reported that, genetic ablation of GRK2 in mice reduced insulin resistance. In this sense, inhibition of GRK2 activity could improve insulin sensitivity and might provide a new therapeutic target for the treatment of IR and T2DM. Paroxetine, an FDA-approved selective serotonin reuptake inhibitor (SSRI), was identified as a potent GRK2 inhibitor with higher selectivity for GRK2 over other GRKs both in vivo and in vitro.
Paroxetine binds to the active site of GRK2 and stabilizes the kinase domain in a conformation that inhibits G protein-coupled receptor (GPCR) phosphorylation and desensitization.6 A case report study demonstrated that during 3 months of paroxetine treatment, 35-year-old woman with poorly controlled T2DM experienced an increased frequency of hypoglycemic episodes. After discontinuation of paroxetine, her awareness of hypoglycemia was dramatically improved. The authors hypothesized that her hypoglycemic unawareness might be caused by autonomic dysfunction, which is an atypical manifestation of serotonin syndrome. Paroxetine also increased insulin sensitivity in non-diabetic patients who experienced remitted depression in a randomized trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This proof of concept pilot study is designed as a randomized placebo controlled parallel trial. Forty four patients of both gender with confirmed diagnosis of T2DM will be randomized using sealed envelope method into two groups
| Arm | Type | Receives |
|---|---|---|
| group 1 (control group) | Placebo comparator | Drug: Placebowhich will receive metformin based combined oral hypoglycemic plus placebo tablets |
| group II (intervention group) | Active comparator | Drug: Paroxetinewhich will receive metformin based combined oral hypoglycemic plus 12.5 mg paroxetine daily at morning. |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients with established diagnosis of type 2 diabetes.
- Patients with type 2 diabetes treated with metformin based combined oral hypoglycemic ( metformin plus DDP4 inhibitor or metformin plus sulfonylureas or metformin plus GLP-1 analogues)
- Glycated hemoglobin (HbA1c) ≥ 7% and ≤9
- Age between 20 and 65 years
- BMI ≥25 kg/m2
Key exclusion criteria (11 listed)
- Pregnant and lactating women
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 |
|---|---|---|
| Paroxetineintervention group n=22 Patients with type 2 diabetes treated with metformin based combined oral hypoglycemic ( metformin plus DDP4 inhibitor or metformin plus sulfonylureas or metformin plus GLP-1 analogues) plus paroxetine 12.5 mg daily | Drug | group II (intervention group) |
| PlaceboPatients with type 2 diabetes treated with metformin based combined oral hypoglycemic ( metformin plus DDP4 inhibitor or metformin plus sulfonylureas or metformin plus GLP-1 analogues) plus placebo daily | Drug | group 1 (control group) |
Primary outcome
The primary outcome is the change in glycated Hemoglobin (HbA1c).
Time frame: 3 months
Change in HOMA-IR .
Time frame: 3 months
1 secondary outcome
The secondary outcome is the change in expression of GRK2
Time frame: 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2024.
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Paroxetine in people with Diabetes Mellitus, Type 2, run by aya ramadan ashmawy sarhan.
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 5 inclusion and 11 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: status not confirmed, as of the sponsor's last update on 12 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
The primary outcome is the change in glycated Hemoglobin (HbA1c). (time frame: 3 months). The study lists 2 primary outcomes in all. 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 12 Jan 2024.