Primary outcomeMean· 6 weeks after start of each intervention
Cytokine Interleukin-6 (IL-6) Messenger Ribonucleic Acid (mRNA) Level (From Adipose Tissue)
| Group | Value (natural log(arbitrary units)) |
|---|---|
| Cyanocobalamin | 7.88 |
| Dulaglutide | 7.67 |
Trial · Interventional
CompletedPhase 4Results postedRegistry dataGLP-1 Therapy: The Role of IL-6 Signaling and Adipose Tissue Remodeling in Metabolic Response
Overview
- Status
- Completed
- Phase
- Phase 4
- Enrollment
- 23 participants (actual)
- Sponsor
- The University of Texas Health Science Center, Houston · Other
- Design
- Not randomized · Open label (no masking)
- Countries
1 country
United States
- Start
- 15 May 2020
- Primary completion
- 6 Oct 2023
- Completion
- 6 Oct 2023
- First posted
- 13 May 2020
- Last update posted
- 5 Dec 2024
- Conditions
- Glucose Intolerance · Overweight and Obesity · Drug Effect · Adiposity
Timeline
1 trial · 1 completed · 1 with posted results
- Completed
- Ongoing
- Not yet recruiting
- Stopped
- Estimated dates (est.)
- Results posted
20202021202220232024
- Ph 4
GLP-1 Therapy: The Role of IL-6 Signaling and Adipose Tissue Remodeling in Metabolic Response
NCT0438720115 May 2020 to 6 Oct 2023
Registry summary
Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.
This project investigates the anti-obesity mechanisms of glucagon-like peptide-1 (GLP-1) analogs, which are used in the treatment of human obesity and diabetes mellitus. The investigators will test if GLP-1 induces secretion of interleukin-6 (IL-6), a cytokine that may collaborate with GLP-1 analogs to induce the formation of brown fat, which has anti-diabetic properties. The results will guide future obesity and diabetes mellitus therapies.
Interventions
- CyanocobalaminDrug
- DulaglutideDrug
Arms2
Experimental
Cyanocobalamin, then Dulaglutide
Participants first received Cyanocobalamin (vitamin B12) 1000 mcg subcutaneous weekly for 6 weeks. After a washout period of 3 weeks, they then received Dulaglutide 0.75 mg subcutaneous weekly for 2 weeks, followed by 1.5 mg subcutaneous weekly for 4 weeks
Experimental
Dulaglutide, then Cyanocobalamin
Participants first received Dulaglutide 0.75 mg subcutaneous weekly for 2 weeks, followed by 1.5 mg subcutaneous weekly for 4 weeks. After a washout period of of 3 weeks, they then Cyanocobalamin (vitamin B12) 1000 mcg subcutaneous weekly for 6 weeks.
Primary outcomes3
Outcomes the sponsor listed as primary.
Cytokine Interleukin-6 (IL-6) Messenger Ribonucleic Acid (mRNA) Level (From Adipose Tissue)
Time frame · 6 weeks after start of each intervention
Registry description
natural log transformed data is reported
Uncoupling Protein 1 (UCP1) Messenger Ribonucleic Acid (mRNA) Level (From Adipose Tissue)
Time frame · 6 weeks after start of each intervention
Registry description
Uncoupling protein 1 (UCP1) is a marker of beige/brown fat. natural log transformed data is reported
Signal Transducer and Activator of Transcription 3 (STAT3) Band Intensity/Western Blot (From Adipose Tissue)
Time frame · 6 weeks after start of each intervention
Registry description
signaling intermediary with interleukin-6
Secondary outcomes(20)
PR Domain Containing 16 (PRDM16) Messenger Ribonucleic Acid (mRNA) Level ((From Adipose Tissue)
Time frame · 6 weeks after start of each intervention
Registry description
PR domain containing 16 (PRDM16) is a marker of beige/brown fat. natural log transformed data is reported.
Nicotinamide Adenine Dinucleotide Dehydrogenase (Ubiquinone) Iron-sulfur protein3 (NDUFS3) (From Adipose Tissue)
Time frame · 6 weeks after start of each intervention
Registry description
marker of beige/brown fat
Beta1-adrenoceptor (ADRB1) (From Adipose Tissue)
Time frame · 6 weeks after start of each intervention
Registry description
marker of beige/brown fat
Beta2-adrenoceptor (ADRB2) (From Adipose Tissue)
Time frame · 6 weeks after start of each intervention
Registry description
marker of beige/brown fat
Beta3-adrenoceptor (ADRB3) (From Adipose Tissue)
Time frame · 6 weeks after start of each intervention
Registry description
marker of beige/brown fat
Nuclear Factor Kappa B (NfKappaB) p65 Band Intensity/Western Blot (From Peripheral Blood Mononuclear Cells)
Time frame · 6 weeks after start of each intervention
Registry description
signaling intermediary with interleukin-6
Interleukin-6 (IL-6) mRNA (From Peripheral Blood Mononuclear Cells)
Time frame · 6 weeks after start of each intervention
Registry description
cytokine
IL-6 (From Peripheral Blood Mononuclear Cells)
Time frame · 6 weeks after start of each intervention
Registry description
cytokine
Suppressor of Cytokine Signaling 3 (SOCS3) Band Intensity/Western Blot (From Peripheral Blood Mononuclear Cells)
Time frame · 6 weeks after start of each intervention
Registry description
signaling intermediary with interleukin-6
Cytokine IL-6 Level (From Plasma)
Time frame · 6 weeks after start of each intervention
Registry description
natural log transformed data is reported. The "Measure Type" indicated as "Mean" actually refers to a "Adjusted Mean." Mean was adjusted for meteorological season. The meteorological season (i.e., spring, summer, fall, and winter) was adjusted for in the multivariable analysis as a potential confounding factor, since imbalances in ambient temperature between study arms could affect the findings.
Free Fatty Acids Level (From Plasma)
Time frame · 6 weeks after start of each intervention
Registry description
Free fatty acids level is a marker for insulin resistance. natural log transformed data is reported The "Measure Type" indicated as "Mean" actually refers to a "Adjusted Mean." Mean was adjusted for meteorological season. The meteorological season (i.e., spring, summer, fall, and winter) was adjusted for in the multivariable analysis as a potential confounding factor, since imbalances in ambient temperature between study arms could affect the findings.
Insulin Level (From Plasma)
Time frame · 6 weeks after start of each intervention
Registry description
Insulin Level is a marker of insulin resistance. natural log transformed data is reported. The "Measure Type" indicated as "Mean" actually refers to a "Adjusted Mean." Mean was adjusted for meteorological season. The meteorological season (i.e., spring, summer, fall, and winter) was adjusted for in the multivariable analysis as a potential confounding factor, since imbalances in ambient temperature between study arms could affect the findings.
Glucose Level (From Plasma)
Time frame · 6 weeks after start of each intervention
Registry description
Glucose Level is a marker of insulin resistance. The "Measure Type" indicated as "Mean" actually refers to a "Adjusted Mean." Mean was adjusted for meteorological season. The meteorological season (i.e., spring, summer, fall, and winter) was adjusted for in the multivariable analysis as a potential confounding factor, since imbalances in ambient temperature between study arms could affect the findings.
Tumor Necrosis Factor - Alpha (From Plasma)
Time frame · 6 weeks after start of each intervention
Registry description
natural log transformed data is reported. The "Measure Type" indicated as "Mean" actually refers to a "Adjusted Mean." Mean was adjusted for meteorological season. The meteorological season (i.e., spring, summer, fall, and winter) was adjusted for in the multivariable analysis as a potential confounding factor, since imbalances in ambient temperature between study arms could affect the findings.
Interleukin-4 (From Plasma)
Time frame · 6 weeks after start of each intervention
Registry description
cytokine
Interleukin-10 (From Plasma)
Time frame · 6 weeks after start of each intervention
Registry description
cytokine
Interleukin-11 (From Plasma)
Time frame · 6 weeks after start of each intervention
Registry description
cytokine
Interleukin-13 (From Plasma)
Time frame · 6 weeks after start of each intervention
Registry description
cytokine
Glucagon-like Peptide-1 (From Plasma)
Time frame · 6 weeks after start of each intervention
Registry description
The "Measure Type" indicated as "Mean" actually refers to a "Adjusted Mean." Mean was adjusted for meteorological season. The meteorological season (i.e., spring, summer, fall, and winter) was adjusted for in the multivariable analysis as a potential confounding factor, since imbalances in ambient temperature between study arms could affect the findings.
Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
Time frame · 6 weeks after start of each intervention
Registry description
Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) is a marker of insulin resistance, calculated according to the formula: fasting insulin (mU/mL) x fasting glucose (mmol/L)/22.5 The "Measure Type" indicated as "Mean" actually refers to a "Adjusted Mean." Mean was adjusted for meteorological season. The meteorological season (i.e., spring, summer, fall, and winter) was adjusted for in the multivariable analysis as a potential confounding factor, since imbalances in ambient temperature between study arms could affect the findings.
Posted results
Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.
Primary outcome results
Primary outcomeMean· 6 weeks after start of each intervention
Uncoupling Protein 1 (UCP1) Messenger Ribonucleic Acid (mRNA) Level (From Adipose Tissue)
| Group | Value (natural log(arbitrary units)) |
|---|---|
| Cyanocobalamin | 1.69 |
| Dulaglutide | 3.78 |
Primary outcome· 6 weeks after start of each intervention
Signal Transducer and Activator of Transcription 3 (STAT3) Band Intensity/Western Blot (From Adipose Tissue)
| Group | Value |
|---|---|
| Cyanocobalamin | not posted |
| Dulaglutide | not posted |
Secondary and other outcome results(5)
Secondary outcomeMean· 6 weeks after start of each intervention
PR Domain Containing 16 (PRDM16) Messenger Ribonucleic Acid (mRNA) Level ((From Adipose Tissue)
| Group | Value (natural log(arbitrary units)) |
|---|---|
| Cyanocobalamin | 2.58 |
| Dulaglutide | 2.53 |
Secondary outcome· 6 weeks after start of each intervention
Nicotinamide Adenine Dinucleotide Dehydrogenase (Ubiquinone) Iron-sulfur protein3 (NDUFS3) (From Adipose Tissue)
| Group | Value |
|---|---|
| Cyanocobalamin | not posted |
| Dulaglutide | not posted |
Secondary outcome· 6 weeks after start of each intervention
Beta1-adrenoceptor (ADRB1) (From Adipose Tissue)
| Group | Value |
|---|---|
| Cyanocobalamin | not posted |
| Dulaglutide | not posted |
Secondary outcome· 6 weeks after start of each intervention
Beta2-adrenoceptor (ADRB2) (From Adipose Tissue)
| Group | Value |
|---|---|
| Cyanocobalamin | not posted |
| Dulaglutide | not posted |
Secondary outcome· 6 weeks after start of each intervention
Beta3-adrenoceptor (ADRB3) (From Adipose Tissue)
| Group | Value |
|---|---|
| Cyanocobalamin | not posted |
| Dulaglutide | not posted |
Adverse events, as posted
| Group | Deaths | Serious events | Other events |
|---|---|---|---|
| CyanocobalaminCyanocobalamin: Cyanocobalamin (vitamin B12) 1000 mcg subcutaneous weekly for 6 weeks. | 0 / 23 | 0 / 23 | 1 / 23 |
| DulaglutideDulaglutide: Dulaglutide 0.75 mg subcutaneous weekly for 2 weeks, followed by 1.5 mg subcutaneous weekly for 4 weeks | 0 / 23 | 0 / 23 | 0 / 23 |
Each cell reads participants affected / participants at risk, as the registry posted them.
Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works
Studies0
Studies that cite this trial.
No study cites this trial.
Eligibility
Who could join, as posted.
- Sex
- All
- Age
- from 18 Years up to 50 Years
- Healthy volunteers
- Not accepted
Inclusion and exclusion criteria, as posted
Inclusion criteria:
1. Men and women, ages 18-50 years
2. Diagnosis of Prediabetes - defined as either impaired fasting glucose (fasting glucose of 100-125 mg/dL), impaired glucose tolerance (2-hour postprandial blood glucose of 140-199 mg/dL after 75-gram oral glucose challenge), and/or a hemoglobin A1C ranging from 5.5% to 6.4%.
3. BMI ≤ 35 kg/m2
4. Women of childbearing age must agree to use an acceptable method of pregnancy prevention (barrier methods, abstinence, oral contraception, vaginal rings, long-acting reversible contraceptives, or surgical sterilization) for the duration of the study
5. Patients must have the following laboratory values: Hematocrit ≥ 33 vol%, estimated glomerular filtration rate ≥ 60 mL/min per 1.73 m2, AST (SGOT) \< 2.5 times ULN, ALT (SGPT) \< 2.5 times ULN, alkaline phosphatase \< 2.5 times ULN
6. If patients are receiving antihypertensive medications (other than beta blockers) and/or lipid-lowering medications, they must remain on stable doses for the duration of the study.
7. If patients are receiving NSAIDs or antioxidant vitamins, these must be discontinued one week prior to study initiation and cannot be restarted during the study.
8. If patient takes thyroid medications, these must be dosed to control hypo- or hyperthyroidism.
Exclusion Criteria:
1. History of Type 1 or Type 2 diabetes mellitus
2. Pregnant or breastfeeding women
3. Medications: Beta blockers, corticosteroids, monoamine oxidase inhibitors, diabetes medications (including incretin mimetics and thiazolidinediones), and/or immunosuppressive therapy over the last 2 months.
4. Uncontrolled hypo- or hyperthyroidism
5. Current tobacco use
6. Active malignancy
7. History of clinically significant cardiac, hepatic, or renal disease.
8. History of any serious hypersensitivity reaction to study medications, any other incretin mimetic, any other formulation of supplemental vitamin B12, and/or cobalt
9. Personal or family history of Leber hereditary optic nerve atrophy
10. Prisoners or subjects who are involuntarily incarcerated
11. Compulsorily detention for treatment of either a psychiatric or physical (e.g., infectious disease) illness
12. Prior history of pancreatitis, medullary thyroid cancer, or multiple endocrine neoplasia type 2 (MEN 2)
13. Serum vitamin B12 level above the upper limit of assay detection
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