Adipose Tissue Heterogeneity and Its Link to Type 2 Diabetes: A Randomized Open Intervention Study That Compares Empagliflozin, Pioglitazone and Semaglutide (DiaSpax)

Start 23 Jan 2023 · Status Authorised, recruiting · 2 EU/EEA countries · 3 sites

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)

Status Authorised, recruiting

Participants planned 90

Countries 2

Sites 3

Diabetes type 2

How do various antidiabetic drugs differ in their beneficial effects on adipose tissue function?

Key facts

Sponsor: Karolinska University Hospital
Participant type: Patients
Age range: 18-64 years, 65+ years
Gender: Male and Female
Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
Trial duration: 23 Jan 2023 → ongoing
Decision date (initial): 2025-03-13
Transition trial: Yes
Low-intervention: No
Rare-disease indication: No
Vulnerable population: No

External identifiers

EU CT number: 2024-513416-98-00
EudraCT number: 2021-002367-21
ClinicalTrials.gov: NCT05501483

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacodynamic

How do various antidiabetic drugs differ in their beneficial effects on adipose tissue function?

Secondary objectives 1

Do the studied antidiabetic drugs have different effects on the cellular composition of adipose tissue (adipose tissue heterogeneity) measured using bulk and single-cell techniques?

Conditions and MedDRA coding

Diabetes type 2

Version	Level	Code	Term	System organ class
20.0	SOC	10027433	Metabolism and nutrition disorders	6
20.0	PT	10012601	Diabetes mellitus	100000004861
21.1	LLT	10045242	Type II diabetes mellitus	10027433

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

The participant has provided written consent to participate in the study
Age 30-70
BMI ≥25
HbA1c ≥42 mmol/mol
Fertile women must use effective contraception throughout the study. Effective contraception includes any of the following: Combined hormonal contraceptives (estrogen and progestogen) that inhibit ovulation: oral, intravaginal, or transdermal; Progestogen-only contraceptives that inhibit ovulation: oral, injectable, or implantable; Intrauterine device (hormonal or copper); Bilateral tubal occlusion; Vasectomized partner; Sexual abstinence (refraining from heterosexual intercourse throughout the study). Women of childbearing potential need a negative pregnancy test at screening before randomization.

Exclusion criteria 17

HbA1C ≥ 65 mmol/mol
Low C-peptide/glucose ratio indicative of endogenous insulin deficiency (less than 2 measured as pmol/mg per dL)
NT-proBNP 20% above the normal reference value
Kidney disease/impairment (eGFR <60 ml/min)
Liver disease and/or impairment (hepatic values over twice the upper reference value)
Other severe chronic illness including ongoing cancer
Established cardiovascular disease and/or heart failure
Severe psychiatric condition
Active alcoholism
Insulin treatment
Waran or NOAK-treatment
Pregnancy, nursing or planned pregnancy
Ongoing pregnancy (positive pregnancy test)
Positive GAD or IA2 antibodies (Above reference range)
Hypersensitivity to the active substance or any of its excipients
History of bladder cancer
Uninvestigated macroscopic hematuria

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

Lipolysis is measured as basal and maximal isoprenaline-stimulated lipolysis in isolated adipocytes from the subcutaneous abdominal periumbilical adipose tissue and expressed as log10 ISO-stimulated/basal glycerol release ex vivo

Secondary endpoints 1

The cellular heterogeneity of adipose tissue (i.e., different adipocyte subtypes) is measured using qPCR of ADIPOQ/LEP in the same adipose tissue samples from which lipolysis is measured.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 8

Rybelsus 7 mg tablets

PRD7996059 · Product

Active substance: Semaglutide
Substance synonyms: NNC0113-0217
Pharmaceutical form: TABLET
Route of administration: ORAL USE
Max daily dose: 14 mg milligram(s)
Max total dose: 14 mg milligram(s)
Max treatment duration: 6 Month(s)
Authorisation status: Authorised
ATC code: A10BJ06 — -
Marketing authorisation: EU/1/20/1430/005
MA holder: NOVO NORDISK A/S
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Rybelsus 3 mg tablets

PRD7996055 · Product

Active substance: Semaglutide
Substance synonyms: NNC0113-0217
Pharmaceutical form: TABLET
Route of administration: ORAL USE
Max daily dose: 14 mg milligram(s)
Max total dose: 14 mg milligram(s)
Max treatment duration: 6 Month(s)
Authorisation status: Authorised
ATC code: A10BJ06 — -
Marketing authorisation: EU/1/20/1430/001
MA holder: NOVO NORDISK A/S
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Rybelsus 14 mg tablets

PRD7996072 · Product

Active substance: Semaglutide
Substance synonyms: NNC0113-0217
Pharmaceutical form: TABLET
Route of administration: ORAL USE
Max daily dose: 14 mg milligram(s)
Max total dose: 14 mg milligram(s)
Max treatment duration: 6 Month(s)
Authorisation status: Authorised
ATC code: A10BJ06 — -
Marketing authorisation: EU/1/20/1430/008
MA holder: NOVO NORDISK A/S
MA country: Iceland
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Jardiance 10 mg film-coated tablets

PRD1594848 · Product

Active substance: Empagliflozin
Pharmaceutical form: FILM-COATED TABLET
Route of administration: ORAL USE
Max daily dose: 25 mg milligram(s)
Max total dose: 25 mg milligram(s)
Max treatment duration: 6 Month(s)
Authorisation status: Authorised
ATC code: A10BK03 — -
Marketing authorisation: EU/1/14/930/010
MA holder: BOEHRINGER INGELHEIM INTERNATIONAL GMBH
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Jardiance 25 mg film-coated tablets

PRD1594891 · Product

Active substance: Empagliflozin
Pharmaceutical form: FILM-COATED TABLET
Route of administration: ORAL USE
Max daily dose: 25 mg milligram(s)
Max total dose: 25 mg milligram(s)
Max treatment duration: 6 Month(s)
Authorisation status: Authorised
ATC code: A10BK03 — -
Marketing authorisation: EU/1/14/930/001
MA holder: BOEHRINGER INGELHEIM INTERNATIONAL GMBH
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Actos 15 mg tablets

PRD9120726 · Product

Active substance: Pioglitazone
Pharmaceutical form: TABLET
Route of administration: ORAL USE
Max daily dose: 45 mg milligram(s)
Max total dose: 45 mg milligram(s)
Max treatment duration: 6 Month(s)
Authorisation status: Authorised
ATC code: A10BG03 — PIOGLITAZONE
Marketing authorisation: EU/1/00/150/001
MA holder: CHEPLAPHARM ARZNEIMITTEL GMBH
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Actos 30 mg tablets

PRD9120883 · Product

Active substance: Pioglitazone
Pharmaceutical form: TABLET
Route of administration: ORAL USE
Max daily dose: 45 mg milligram(s)
Max total dose: 45 mg milligram(s)
Max treatment duration: 6 Month(s)
Authorisation status: Authorised
ATC code: A10BG03 — PIOGLITAZONE
Marketing authorisation: EU/1/00/150/004
MA holder: CHEPLAPHARM ARZNEIMITTEL GMBH
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Actos 45 mg tablets

PRD9121095 · Product

Active substance: Pioglitazone
Pharmaceutical form: TABLET
Route of administration: ORAL USE
Max daily dose: 45 mg milligram(s)
Max total dose: 45 mg milligram(s)
Max treatment duration: 6 Month(s)
Authorisation status: Authorised
ATC code: A10BG03 — PIOGLITAZONE
Marketing authorisation: EU/1/00/150/012
MA holder: CHEPLAPHARM ARZNEIMITTEL GMBH
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Karolinska University Hospital

Sponsor organisation: Karolinska University Hospital
Address: Halsovagen, Flemingsberg Flemingsberg
City: Huddinge
Postcode: 141 86
Country: Sweden

Scientific contact point

Organisation: Karolinska University Hospital
Contact name: Principal Investigator

Public contact point

Organisation: Karolinska University Hospital
Contact name: Principal Investigator

Third parties 1

Organisation	City, country	Duties
Frederiksberg Hospital ORG-100028217	Frederiksberg, Denmark	On site monitoring

Locations

2 EU/EEA countries · 3 investigational sites

By country

Country	MS status	Planned subjects	Sites
Denmark	Authorised, recruitment pending	30	2
Sweden	Ongoing, recruiting	60	1
Rest of world	—	0	—

Investigational sites

Denmark

2 sites · Authorised, recruitment pending

Steno Diabetes Center Copenhagen

Translational Type 2-Diabetes Research, Borgmester Ib Juuls Vej 83, 2730, Herlev

Aarhus University Hospital

Institute for Clinical Medicine - SDCA, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N

Sweden

1 site · Ongoing, recruiting

Karolinska University Hospital

ME Endokrinologi, C2-94, Karolinska Universitetssjukhuset, Huddinge, Halsovagen, Flemingsberg, Huddinge

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country	Trial start	Trial end	Recruitment start	Recruitment end	Early termination
Sweden	2023-01-23		2023-01-23

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 40 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Type	Title	Version
Protocol (for publication)	Diaspax protocol_clean	10.0
Protocol (for publication)	Diaspax protocol_track changes	7
Protocol (for publication)	DiaSpax studieprotokoll v 6 20240319	6
Protocol (for publication)	Survey A Health Declaration	1
Protocol (for publication)	Survey A Health Declaration Danish	1
Protocol (for publication)	Survey B Heredity	1
Protocol (for publication)	Survey B Heredity Danish	1
Protocol (for publication)	Survey C BITE	1
Protocol (for publication)	Survey C BITE Danish	1
Protocol (for publication)	Survey D RAND-36	1
Protocol (for publication)	Survey D RAND-36 Danish	1
Recruitment arrangements (for publication)	Blankt dokument	1
Recruitment arrangements (for publication)	K_1 Recruitment arrangements	1
Recruitment arrangements (for publication)	K1_ Recruitment Arrangements	2.0
Recruitment arrangements (for publication)	K2_ Recruitment Arrangements_ Flyer	2.0
Recruitment arrangements (for publication)	K2_ Recruitment Arrangements_ Poster	2.0
Recruitment arrangements (for publication)	K2_ Recruitment Material_ Mail GP	2.0
Recruitment arrangements (for publication)	K2_ Recruitment Material_ Trialtree	2.0
Recruitment arrangements (for publication)	K2_ Recruitment Material_Mail Cohort	2.0
Recruitment arrangements (for publication)	K2_Recruitment material description	1
Subject information and informed consent form (for publication)	L1_ ICF	2.0
Subject information and informed consent form (for publication)	L1_ ICF Future Research	2.0
Subject information and informed consent form (for publication)	L1_ SIS	2.0
Subject information and informed consent form (for publication)	L1_SIS and ICF description	6.0
Subject information and informed consent form (for publication)	L2 _ Your rights as a participant	1
Subject information and informed consent form (for publication)	Samtycke_diaspax_2024-01-31	2
Summary of Product Characteristics (SmPC) (for publication)	Actos pioglitazon SmPC	1
Summary of Product Characteristics (SmPC) (for publication)	Jardiance empagliflozin SmPC	1
Summary of Product Characteristics (SmPC) (for publication)	Rybelsus semaglutide SmPC	1
Summary of Product Characteristics (SmPC) (for publication)	SmPC Actos_dansk	1
Summary of Product Characteristics (SmPC) (for publication)	SmPC Actos_eng	1
Summary of Product Characteristics (SmPC) (for publication)	SmPC Jardiance_dansk	1
Summary of Product Characteristics (SmPC) (for publication)	SmPC Jardiance_eng	1
Summary of Product Characteristics (SmPC) (for publication)	SmPC Rybelsus_dansk	1
Summary of Product Characteristics (SmPC) (for publication)	SmPC Rybelsus_eng	1
Synopsis of the protocol (for publication)	D1_Protocol synopsis_DK 2024-513416-98	2
Synopsis of the protocol (for publication)	D1_Protocol synopsis_SWE 2024-513416-98	10
Synopsis of the protocol (for publication)	DiaSpax synopsis	6
Synopsis of the protocol (for publication)	DiaSpax synopsis_clean	7
Synopsis of the protocol (for publication)	DiaSpax synopsis_track_changes	7

Application history

5 submissions — initial application plus substantial / non-substantial modifications

#	Type	Code	Submitted	Reference MS	Conclusion	Decision date
1	INITIAL	IN	2024-05-29	Sweden	Acceptable 2024-06-11	2024-06-11
2	SUBSTANTIAL MODIFICATION	SM-2	2024-10-02	Sweden	Acceptable 2024-11-26	2024-11-26
3	SUBSEQUENT ADDITION OF MSC	APP-3	2024-12-16			2025-03-13
4	SUBSTANTIAL MODIFICATION	SM-3	2025-03-25	Sweden	Acceptable 2025-05-13	2025-05-13
5	SUBSTANTIAL MODIFICATION	SM-4	2025-09-11	Sweden	Acceptable 2025-11-13	2025-11-14

Adipose Tissue Heterogeneity and Its Link to Type 2 Diabetes: A Randomized Open Intervention Study That Compares Empagliflozin, Pioglitazone and Semaglutide (DiaSpax)

Overview

Key facts

External identifiers

Trial design

Main objective

Secondary objectives 1

Conditions and MedDRA coding

Eligibility criteria

Inclusion criteria 5

Exclusion criteria 17

Endpoints

Primary endpoints 1

Secondary endpoints 1

Investigational products

Test 8

Sponsors and contacts

Karolinska University Hospital

Scientific contact point

Public contact point

Third parties 1

Locations

By country

Investigational sites

Country notifications

Results and documents

Documents 40 files

Application history

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