Adaptive Mechanisms In GRown up ObeSity Study (AMIGROS)

Obesity Clinical Trial

— AMIGROS  

Official title:

Mechanistic Studies in Human Subcutaneous Adipose Tissue

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06065930
• Other study ID #: 2023-02051-02
• Status: Recruiting
• Start date: May 5, 2023
• Est. completion date: December 31, 2028

Study information

• Verified date: May 2023
• Source: Vastra Gotaland Region
• Contact: Per-Anders E Jansson, Prof
• Phone: 46 70 203 30 10
• Email: per-anders.jansson[@]wlab.gu.se
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The investigator recently showed that the glycan-binding adipokine galectin-1 increased during overfeeding and that galectin-1 independently could predict type 2 diabetes. Further, the molecules that induce insulin release in the fasting state when blood glucose is normal remain elusive. It is possible that galectin-1 is involved in adaptive mechanisms in adipose tissue in obese subjects.

Description:

The investigator will define adaptive mechanisms in adipose tissue associated with galectin-1 in obese insulin-sensitive (Ob-IS) subjects compared with obese insulin-resistant (Ob-IR) subjects and lean healthy controls. Further, the investigator will study molecules secreted from adipose tissue that might trigger insulin secretion when blood glucose is normal. The investigator hypothesizes that Ob-IS subjects keep fatty acid levels normal through an adaptive response in adipose tissue that involves up-regulation of galectin-1 for dampening of immune cell activity and stimulation of lipolysis.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: December 31, 2028
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Men and women of age: 40.0 - 70.0 years

2. BMI: 18.0 - 25.0 kg/m2 (lean subjects) and BMI 30.0 - 38.0 kg/m2 (Ob-IS and Ob-IR)

3. Fasting insulin < 9.0 mU/l (lean and Ob-IS subjects) and fasting insulin > 9.0 mU/l (Ob-IR)

4. Fasting glucose < 6.1 mmol/l

5. Body temperature < 37.5°C

6. First-degree relative with known T2D in Ob-IR

7. Weight stable ± 5 kg < 3 months before screening

8. Fluent in Swedish and can follow given instructions

9. Consent given to participate

Exclusion Criteria:

10. First-degree relative with known T2D in lean or Ob-IS subjects

11. Alcohol intake > 10 units/week or known high alcohol intake < 10 years back in time

12. Daily use of cigarettes or daily frequent use of smokeless tobacco not enabling the participant to suspend nicotine during a visit at the research center without getting abstinent

13. Regular physical activity corresponding to Saltin-Gimby level 4

14. Special diet eg Atkins or 5:2 for weight reduction. Vegetarian food accepted if duration > 1 year

15. Impaired fasting glucose (IFG) (venous fasting plasma glucose 6.1-6.9 mmol/l)

16. Type 2 diabetes according to ADA criteria

17. Ongoing or previous ischemic heart disease, eg angina pectoris, unstable angina or previous myocardial infarction treated with platelet inhibitors or non vitamin-K oral anticoagulants

18. Heart failure (NYHA II-IV) or cardiac arrhytmia that needs medical treatment

19. Previous cerebral infarction or transitory ischemic episodes (TIA) treated with platelet inhibitors or other anticoagulants

20. Peripheral arterial insufficiency eg claudication

21. Hypertension >170/105 mmHg at screening or more than one class of drugs for treatment of known hypertension

22. Lipid disorder defined as fasting serum triglycerides > 5.0 mmol/l or serum cholesterol > 7.5 mmol/l

23. Hematologic diseases such as anemia not being substituted (Hb < 130 g/l in males and Hv < 120 g/l in females) or disease causing bleeding disorder

24. Renal failure defined as absolute estimated glomerular filtration rate (eGFRcreatinine) < 60 ml/min/1.73 m2

25. Hypothyroidism defined as TSH > 4.0 mIE/l and symptoms

26. Liver disease e.g. hepatitis B, cirrhosis or conditions where AST or ALT are > 2 times UNL

27. Systemic inflammatory disease e.g. rheumatoid arthritis, ulcerative cholitis or Chrons disease. Celiac disease, dyspepsia or IBS are excepted

28. Chronic bronchitis or chronic obstructive pulmonary with disease symptoms

29. Previous pancreatitis or other disease in pancreas that needs treatment

30. Migraine elicited by stress

31. Spinal insufficiency causing inconvenience lying in supine position during the study day

32. Drug addiction interfering with the study procedures

33. Psychiatric insufficiency interfering with the study procedures

34. Medication with potential to affect adipose tissue metabolism that can not be stopped 10 days before the study days

35. Treatment with beta-blockers

36. Less than three months from previous use of antibiotics

37. Cancer disease < 5 years since diagnosis

38. Physical examination or laboratory results indicating that participation in the study is inappropriate

39. Pregnancy or intention to be pregnant during the study

40. Shift work > 1 time per week that might interfere with the circadian rhytm

41. Other reasons that causes the PI to believe that participation is inappropriate

Related Conditions & MeSH terms

• Obesity
• Type 2 Diabetes

Intervention

Device:
• Subcutaneous microdialysis
Group with Ob-IS participants, collection of abdominal subcutaneous interstitial dialysates after an overnight´s fast for later measurements of metabolites and peptides eg galectin-1. Group with Ob-IR participants, collection of abdominal subcutaneous interstitial dialysates after an overnight´s fast for later measurements of metabolites and peptides eg galectin-1. Group with Leans, collection of abdominal subcutaneous interstitial dialysates after an overnight´s fast for later measurements of metabolites and peptides eg galectin-1.

Locations

Country	Name	City	State
Sweden	Gothia Forum CTC	Gothenburg	Region Vastra Gotaland

Sponsors (2)

Lead Sponsor	Collaborator
Vastra Gotaland Region	Göteborg University

Country where clinical trial is conducted

Sweden, 

References & Publications (4)

Drake I, Fryk E, Strindberg L, Lundqvist A, Rosengren AH, Groop L, Ahlqvist E, Boren J, Orho-Melander M, Jansson PA. The role of circulating galectin-1 in type 2 diabetes and chronic kidney disease: evidence from cross-sectional, longitudinal and Mendelia — View Citation

Fryk E, Olausson J, Mossberg K, Strindberg L, Schmelz M, Brogren H, Gan LM, Piazza S, Provenzani A, Becattini B, Lind L, Solinas G, Jansson PA. Hyperinsulinemia and insulin resistance in the obese may develop as part of a homeostatic response to elevated — View Citation

Fryk E, Silva VRR, Jansson PA. Galectin-1 in Obesity and Type 2 Diabetes. Metabolites. 2022 Sep 30;12(10):930. doi: 10.3390/metabo12100930. — View Citation

Fryk E, Sundelin JP, Strindberg L, Pereira MJ, Federici M, Marx N, Nystrom FH, Schmelz M, Svensson PA, Eriksson JW, Boren J, Jansson PA. Microdialysis and proteomics of subcutaneous interstitial fluid reveals increased galectin-1 in type 2 diabetes patien — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fasting galectin-1 concentration in subcutaneous interstitial fluid	Comparison between eligible Ob-IS and Ob-IR subjects < 3 weeks after enrolment	Three weeks
Primary	Fasting Neuropilin-1 concentration in subcutaneous interstitial fluid	Comparison between eligible Ob-IS and Ob-IR subjects < 3 weeks after enrolment	Three weeks
Secondary	Fasting serum galectin-1 concentrations	Comparison between eligible Ob-IS and Ob-IR subjects < 3 weeks after enrolment	Three weeks
Secondary	Fasting serum neuropilin-1 concentrations	Comparison between eligible Ob-IS and Ob-IR subjects < 3 weeks after enrolment	Three weeks
Secondary	Fasting fatty acid levels in subcutaneous dialysates	Comparison between eligible Ob-IS and Ob-IR subjects < 3 weeks after enrolment	Three weeks
Secondary	Fasting plasma fatty acid concentrations	Comparison between eligible Ob-IS and Ob-IR subjects < 3 weeks after enrolment	Three weeks
Secondary	Fasting amino acid profile in subcutaneous dialysates	Comparison between eligible Ob-IS and Ob-IR subjects < 3 weeks after enrolment	Three weeks
Secondary	Fasting serum amino acid concentrations	Comparison between eligible Ob-IS and Ob-IR subjects < 3 weeks after enrolment	Three weeks
Secondary	Circulating metabolome including lipoprotein-related parameters measured by Mass Spectrometry	Comparison between eligible Ob-IS and Ob-IR subjects < 3 weeks after enrolment	Three weeks
Secondary	Circulating lipidome including lipid derivatives measured by Mass Spectrometry	Comparison between eligible Ob-IS and Ob-IR subjects < 3 weeks after enrolment	Three weeks
Secondary	Peptides identified by Mass Spectrometry in subcutaneous dialysates	Comparison between eligible Ob-IS and Ob-IR subjects < 3 weeks after enrolment	Three weeks
Secondary	Ectopic lipid accumulation assessed by magnetic resonance imaging in relative measures	Comparison between eligible Ob-IS and Ob-IR subjects < 9 weeks after enrolment	Nine weeks
Secondary	RNA sequencing results of subcutaneous adipose cells	Comparison between eligible Ob-IS and Ob-IR subjects < 6 weeks after enrolment	Six weeks
Secondary	Function of immune cells in subcutaneous stromal vascular fraction characterized by Fluorescence Activated Cell Sorting (FACS)	Comparison between eligible Ob-IS and Ob-IR subjects < 6 weeks after enrolment	Six weeks
Secondary	Activation of insulin signaling proteins in adipose cells assessed by Western blot	Comparison between eligible Ob-IS and Ob-IR subjects < 6 weeks after enrolment	Six weeks
Secondary	Function of microvascular endothelial cells in subcutaneous stromal vascular fraction	Comparison between eligible Ob-IS and Ob-IR subjects < 6 weeks after enrolment	Six weeks
Secondary	Messenger RNA expression in whole adipose tissue	Comparison between eligible Ob-IS and Ob-IR subjects < 6 weeks after enrolment	Six weeks
Secondary	Dysbiosis in faeces assessed by 16S rRNA gene sequencing	Comparison between eligible Ob-IS and Ob-IR subjects < 6 weeks after enrolment	Six weeks
Secondary	Metabolites in urine including acylcarnitines measured by Mass Spectrometry	Comparison between eligible Ob-IS and Ob-IR subjects < 3 weeks after enrolment	Three weeks