Iatrogenic Cushing's DiseasePhase 2TICSINCT03111810

Targeting Iatrogenic Cushing's Syndrome With 11β-hydroxysteroid Dehydrogenase Type 1 Inhibition

A Phase 2 study testing AZD4017 and prednisolone in people with Iatrogenic Cushing's Disease, run by University of Oxford at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 60 years, men onlyHealthy volunteers can take part
Conditions the study is for: Iatrogenic Cushing's Disease
What is being tested?: AZD4017 and prednisolone
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 32 participants
Where: 1 siteUnited Kingdom
Study dates: 25 May 2017to 1 Aug 2020
Phase: Phase 2
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 18 to 60 years
Men only
Healthy volunteers accepted
Adult

Who may be able to join

The following criteria apply to both arms and each volunteer who has a successful screening visit will be randomized to one of the arms defined above (see section 6): We estimate that we will need to screen 40-50 patients in order to achieve our recruitment target.
Male volunteers without diabetes (HbA1C < 48mmol/mol at screening)
BMI 20-30kg/m2
Age 18-60years
For individuals identified from Oxford Biobank - fasting insulin and / or glucose and / or insulin resistance as measured by Homeostatic model assessment (HOMA) - insulin resistance in the 40th-60th percentile
BP<160/100 mmHg with stable antihypertensive therapy for >3 months

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Stable lipid lowering therapy for >3 months
No contraindications to AZD4017 or prednisolone treatment Study participants who are sexually active with a female partner of childbearing potential must be surgically sterilized, practicing true abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence, e.g. calendar, ovulation, symptothermal, post-ovulation methods, declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception) or agree, along with their partners, to use two forms of highly effective methods of birth control (i.e. condom plus another highly effective method defined below), and not rely on barrier methods and spermicide alone, from the time of screening and for the duration of the study. For the proposed clinical study, all study subjects will be male.
For male study subjects whose partner is pregnant, or whose partner is a woman of child-bearing potential (WOCBP) who is established on and continuing to use a highly effective method of contraception, in addition to the stipulations above, males should continue to use a condom (in addition to the highly effective method) for 1 week following the last dose of study drug (5 drug elimination half-lives rounded up to 1 week).
For male study subjects whose partner is not pregnant but is a WOCBP who is not established on and continuing to use a highly effective method of contraception, males should continue to use a condom (in addition to the highly effective method) for 3 weeks following the last dose of study drug (5 drug elimination half-lives plus 2 weeks).
Male study participants must also not donate sperm from the time of screening until 3 weeks after final dose of study drug (5 drug elimination half-lives plus 2 weeks).
Highly effective methods of contraception are defined as combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (either oral, intravaginal or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (either oral [specifically Cerazette™], injectable or implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner or sexual abstinence.
We would advise that competitive elite athletes do not take part in the study as there is the possibility that the prednisolone could impact upon their athletic performance

Who cannot join

The participant may not enter the study if any of the following apply:
Age <18 or >60years
Body mass index <20 or >30kg/m2
A diagnosis of diabetes (type 1 or type 2)
A blood haemoglobin <120mg/dL
Haemorrhagic disorders

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Anticoagulant treatment
Renal impairment with estimated Glomerular Filtration Rate <60ml/min
Abnormal liver chemistry with aspartate aminotransferase, alanine transaminase and/or Gamma-glutamyltransferase and/or bilirubin more than the upper limit of normal
Glucocorticoid therapy (including inhaled, topical or oral) within the last 6 months
Concomitant anti-inflammatory medication including NSAIDs, disease modifying anti-rheumatic drugs (DMARDs) / steroid-sparing medications (e.g. methotrexate, sulphasalazine, hydroxychloroquine, azathioprine, leflunomide, biologics [anti-Tumor necrosis factor alpha, interleukin-1ra]).
Any medical condition in the opinion of the investigator that might impact upon safety or validity of the results - recent (within 2 weeks) or active infection, known liver disease, known thyroid disease, active malignancy, existing inflammatory condition (e.g. inflammatory arthropathy, inflammatory bowel disease, autoimmune disease, connective tissue disease)
Current evidence of alcohol abuse or a significant history of alcohol abuse, as judged by the investigator.
Contraindication to any of the study treatments or known or suspected hypersensitivity to the investigational product, compounds of the same class, other study treatments or any excipients.
Unwilling, or unable, to give informed consent.
Participation in another investigational medicinal product trial / study within the past 6 months

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

University of Oxford
Oxford

Other trials in United Kingdom

About this study

Official title: Targeting Iatrogenic Cushing's Syndrome With 11β-hydroxysteroid Dehydrogenase Type 1 Inhibition (TICSI)

Currently, 2-3% of the population of the United Kingdom and United States of America receive glucocorticoid therapy. Significant adverse effects are not confined to chronic use; recurrent short-course administration is associated with increased morbidity and mortality. The adverse metabolic features associated with glucocorticoid use include obesity, skeletal muscle myopathy, hypertension, insulin resistance and diabetes and are collectively termed 'iatrogenic Cushing's syndrome'. The efficacy of glucocorticoid therapy is not in doubt, but there are no interventions to reduce their metabolic consequences. Within metabolic tissues (liver, skeletal muscle, adipose), 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates active glucocorticoid and therefore is able to tightly control the availability of glucocorticoids to activate the glucocorticoid receptor. In preclinical studies, the investigators have shown that 11β-HSD1 is critical in regulating the development of the adverse features associated with circulating glucocorticoid excess, endorsing our observations in a patient with Cushing's disease, who was protected from a classical phenotype due to a functional deficit in 11β-HSD1.

This study is the first clinical evaluation of the impact of the selective 11β-HSD1 inhibitor, AZD4017, in healthy volunteers taking exogenous glucocorticoids (prednisolone). The investigators propose that in tissues expressing high levels of 11β-HSD1, prednisolone action will be amplified, driving adverse effects within these tissues and have hypothesized that AZD4017 in humans will reduce the adverse metabolic consequences of Prednisolone administration without compromise to its anti-inflammatory action.

Our specific research objectives are:

To demonstrate the beneficial effect of the selective 11β-HSD1 inhibitor, AZD4017, upon the prednisolone-induced deterioration in metabolic phenotype, including glucose disposal and endogenous glucose production rates.
To determine the impact of AZD4017 on the anti-inflammatory actions of Prednisolone.
To identify the tissue-specific (skeletal muscle, adipose) mechanisms underpinning the response to Prednisolone therapy administered in conjunction with AZD4017.

The investigators will perform a randomized, double-blind placebo controlled study to determine if co-administration of the selective 11β-HSD1 inhibitor, AZD4017, limits the adverse effects of short-course exogenous glucocorticoid administration. 32 healthy male volunteers will have detailed metabolic investigations including 2-step hyperinsulinaemic euglycaemic clamps (with stable isotope measurements of lipid and carbohydrate metabolism), as well as assessment of skeletal muscle forearm glucose uptake. All volunteers will then be treated with Prednisolone (20mg daily) and randomized to the co-administration of placebo or AZD4017. After 1 week of therapy, all investigations will be repeated. Our hypothesis is that the adverse metabolic effects of Prednisolone will be reduced by co-administration of AZD4017.

Conditions: Iatrogenic Cushing's Disease
Being tested: AZD4017 and prednisolone, Placebo Oral Tablet and prednisolone
Keywords: Corticosteroids, Prednisolone, 11 beta-Hydroxysteroid dehydrogenase1 inhibitor, Iatrogenic Cushing's disease, AZD4017

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AZD4017 and prednisoloneDrug
Also called 11 beta-Hydroxysteroid dehydrogenase inhibitor
The drug AZD4017 will be given together with prednisolone 20mg daily for 7 days to compare its effects on metabolic tissues against the placebo arm where the participants will take placebo and prednisolone 20mg daily for 7 days.
Placebo Oral Tablet and prednisoloneDrug
Also called Placebo
Placebo Oral tablet will be given together with prednisolone 20mg daily for 7 days to compare the effects on metabolic tissues of AZD4017 and prednisolone 20mg daily against the placebo arm.

Study groups in NCT03111810
Study group	Role	What they receive
Active	Active comparator	Prednisolone 20mg once daily and AZD4017 400mg twice daily for 7 days. Receives: Drug: AZD4017 and prednisolone
Placebo Oral Tablet	Placebo comparator	Prednisolone 20mg once daily and placebo twice daily for 7 days. Receives: Drug: Placebo Oral Tablet and prednisolone

What is being measured

The primary outcome is the main question the study is designed to answer.

Changes in the detrimental side effects of prednisolone by AZD4017.
To evaluate whether AZD4017 can limit the detrimental effect of prednisolone (20mg) on glucose disposal. This will be achieved by measuring glucose disposal during a hyperinsulinaemic euglycaemic clamp.
Measured: 2 years

Secondary outcomes (9)

Changes in hepatic insulin sensitivity by AZD4017 when given with prednisolone (20mg) compared to prednisolone (20mg) given alone.
Measurement of endogenous glucose production rate during a hyperinsulinaemic euglycaemic clamp.
Measured: 2 years
Changes in blood pressure associated with prednisolone and AZD4017 administration
The participants will have 24h ambulatory blood pressure measurements taken.
Measured: 2 years
Changes in adipose tissue gene expression profile associated with prednisolone and AZD4017 administration.
Gene expression changes will be measured from adipose tissue biopsies.
Measured: 2 years
Change in whole body oxidation associated with prednisolone and AZD4017 administration
Measurement of incorporation of carbon-13 into breath carbon dioxide using Gas chromatography combustion isotope ratio mass spectrometry.
Measured: 2 years
Changes in skeletal muscle gene expression profile associated with prednisolone and AZD4017 administration.
Gene expression changes measured in skeletal muscle biopsies.
Measured: 2 years
Changes in circulating inflammatory cytokines and inflammatory response in circulating inflammatory cells associated with prednisolone and AZD4017 administration.
Measurement of inflammatory cytokines, isolation of peripheral blood mononuclear cells and defining their response to inflammatory stress.
Measured: 2 years
Changes in bone turnover associated with prednisolone and AZD4017 administration.
Measurement of serum and urine markers of bone turnover including type I collagen cross-linked N-telopeptide and osteocalcin
Measured: 2 years
Changes in body composition (total and regional lean and fat mass) associated with prednisolone and AZD4017 administration.
Measurement of total and regional lean and fat mass on dual energy x-ray absorptiometry scan.
Measured: 2 years
Changes in urinary steroid metabolite profile associated with prednisolone and AZD4017 administration.
Steroid metabolites measured by gas chromatography, mass spectrometry in a timed overnight urine sample.
Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

25 May 20171 Aug 2020

First posted13 Apr 2017
Study start25 May 2017
Primary completion1 Aug 2020
Study completion1 Aug 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (9)Papers the sponsor has linked to this study.
Other trials for Iatrogenic Cushing's DiseaseStudies of the same condition, open and under way.
More trials run by University of OxfordThe sponsor's other registered studies.
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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 32 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03111810
Sponsor's protocol ID: 212634
Acronym: TICSI
Status last verified: Mar 2021
First submitted: 17 Mar 2017
Last updated: 13 May 2021
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

van Staa TP, Leufkens HG, Abenhaim L, Begaud B, Zhang B, Cooper C. Use of oral corticosteroids in the United Kingdom. QJM. 2000 Feb;93(2):105-11. doi: 10.1093/qjmed/93.2.105.
PubMed 10700481
Overman RA, Yeh JY, Deal CL. Prevalence of oral glucocorticoid usage in the United States: a general population perspective. Arthritis Care Res (Hoboken). 2013 Feb;65(2):294-8. doi: 10.1002/acr.21796.
PubMed 22807233
Gathercole LL, Lavery GG, Morgan SA, Cooper MS, Sinclair AJ, Tomlinson JW, Stewart PM. 11beta-Hydroxysteroid dehydrogenase 1: translational and therapeutic aspects. Endocr Rev. 2013 Aug;34(4):525-55. doi: 10.1210/er.2012-1050. Epub 2013 Apr 23.
PubMed 23612224
Morgan SA, McCabe EL, Gathercole LL, Hassan-Smith ZK, Larner DP, Bujalska IJ, Stewart PM, Tomlinson JW, Lavery GG. 11beta-HSD1 is the major regulator of the tissue-specific effects of circulating glucocorticoid excess. Proc Natl Acad Sci U S A. 2014 Jun 17;111(24):E2482-91. doi: 10.1073/pnas.1323681111. Epub 2014 Jun 2.
PubMed 24889609
Tomlinson JW, Draper N, Mackie J, Johnson AP, Holder G, Wood P, Stewart PM. Absence of Cushingoid phenotype in a patient with Cushing's disease due to defective cortisone to cortisol conversion. J Clin Endocrinol Metab. 2002 Jan;87(1):57-62. doi: 10.1210/jcem.87.1.8189.
PubMed 11788623
Scott JS, Bowker SS, Deschoolmeester J, Gerhardt S, Hargreaves D, Kilgour E, Lloyd A, Mayers RM, McCoull W, Newcombe NJ, Ogg D, Packer MJ, Rees A, Revill J, Schofield P, Selmi N, Swales JG, Whittamore PR. Discovery of a potent, selective, and orally bioavailable acidic 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitor: discovery of 2-[(3S)-1-[5-(cyclohexylcarbamoyl)-6-propylsulfanylpyridin-2-yl]-3-piperidyl]acetic acid (AZD4017). J Med Chem. 2012 Jun 28;55(12):5951-64. doi: 10.1021/jm300592r. Epub 2012 Jun 19.
PubMed 22691057
Hazlehurst JM, Gathercole LL, Nasiri M, Armstrong MJ, Borrows S, Yu J, Wagenmakers AJ, Stewart PM, Tomlinson JW. Glucocorticoids fail to cause insulin resistance in human subcutaneous adipose tissue in vivo. J Clin Endocrinol Metab. 2013 Apr;98(4):1631-40. doi: 10.1210/jc.2012-3523. Epub 2013 Feb 20.
PubMed 23426618
Tripathy D, Daniele G, Fiorentino TV, Perez-Cadena Z, Chavez-Velasquez A, Kamath S, Fanti P, Jenkinson C, Andreozzi F, Federici M, Gastaldelli A, Defronzo RA, Folli F. Pioglitazone improves glucose metabolism and modulates skeletal muscle TIMP-3-TACE dyad in type 2 diabetes mellitus: a randomised, double-blind, placebo-controlled, mechanistic study. Diabetologia. 2013 Oct;56(10):2153-63. doi: 10.1007/s00125-013-2976-z. Epub 2013 Jun 30.
PubMed 23811853
Gomez C, Alimajstorovic Z, Othonos N, Winter DV, White S, Lavery GG, Tomlinson JW, Sinclair AJ, Odermatt A. Identification of a human blood biomarker of pharmacological 11beta-hydroxysteroid dehydrogenase 1 inhibition. Br J Pharmacol. 2024 Mar;181(5):698-711. doi: 10.1111/bph.16251. Epub 2023 Oct 19.
PubMed 37740611

Study at a glance

From the registry record, last updated by the sponsor on 13 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Targeting Iatrogenic Cushing's Syndrome With 11β-hydroxysteroid Dehydrogenase Type 1 Inhibition (TICSI)
ClinicalTrials.gov ID: NCT03111810
Acronym / sponsor ID: TICSI / 212634
Conditions: Iatrogenic Cushing's Disease
Keywords: Corticosteroids, Prednisolone, 11 beta-Hydroxysteroid dehydrogenase1 inhibitor, Iatrogenic Cushing's disease, AZD4017
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 32 participants (actual)
Lead sponsor: University of OxfordUniversity, hospital or other
Collaborators: AstraZeneca
Study start: 25 May 2017 (actual)
Primary completion: 1 Aug 2020 (actual)
Study completion: 1 Aug 2020 (actual)
First posted: 13 Apr 2017 (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.

Our specific research objectives are:

To demonstrate the beneficial effect of the selective 11β-HSD1 inhibitor, AZD4017, upon the prednisolone-induced deterioration in metabolic phenotype, including glucose disposal and endogenous glucose production rates.
To determine the impact of AZD4017 on the anti-inflammatory actions of Prednisolone.
To identify the tissue-specific (skeletal muscle, adipose) mechanisms underpinning the response to Prednisolone therapy administered in conjunction with AZD4017.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
Active	Active comparator	Drug: AZD4017 and prednisolonePrednisolone 20mg once daily and AZD4017 400mg twice daily for 7 days.
Placebo Oral Tablet	Placebo comparator	Drug: Placebo Oral Tablet and prednisolonePrednisolone 20mg once daily and placebo twice daily for 7 days.

Who may qualify

Ages: 18 to 60 years
Sex: Male only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (13 listed)

The following criteria apply to both arms and each volunteer who has a successful screening visit will be randomized to one of the arms defined above (see section 6): We estimate that we will need to screen 40-50 patients in order to achieve our recruitment target.
Male volunteers without diabetes (HbA1C < 48mmol/mol at screening)
BMI 20-30kg/m2
Age 18-60years
For individuals identified from Oxford Biobank - fasting insulin and / or glucose and / or insulin resistance as measured by Homeostatic model assessment (HOMA) - insulin resistance in the 40th-60th percentile

Key exclusion criteria (16 listed)

Age <18 or >60years
Body mass index <20 or >30kg/m2
A diagnosis of diabetes (type 1 or type 2)
A blood haemoglobin <120mg/dL
Haemorrhagic disorders

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
AZD4017 and prednisoloneAlso: 11 beta-Hydroxysteroid dehydrogenase inhibitorThe drug AZD4017 will be given together with prednisolone 20mg daily for 7 days to compare its effects on metabolic tissues against the placebo arm where the participants will take placebo and prednisolone 20mg daily for 7 days.	Drug	Active
Placebo Oral Tablet and prednisoloneAlso: PlaceboPlacebo Oral tablet will be given together with prednisolone 20mg daily for 7 days to compare the effects on metabolic tissues of AZD4017 and prednisolone 20mg daily against the placebo arm.	Drug	Placebo Oral Tablet

Primary outcome

Changes in the detrimental side effects of prednisolone by AZD4017.
Time frame: 2 years
To evaluate whether AZD4017 can limit the detrimental effect of prednisolone (20mg) on glucose disposal. This will be achieved by measuring glucose disposal during a hyperinsulinaemic euglycaemic clamp.

9 secondary outcomes

Changes in hepatic insulin sensitivity by AZD4017 when given with prednisolone (20mg) compared to prednisolone (20mg) given alone.
Time frame: 2 years
Changes in blood pressure associated with prednisolone and AZD4017 administration
Time frame: 2 years
Changes in adipose tissue gene expression profile associated with prednisolone and AZD4017 administration.
Time frame: 2 years
Change in whole body oxidation associated with prednisolone and AZD4017 administration
Time frame: 2 years
Changes in skeletal muscle gene expression profile associated with prednisolone and AZD4017 administration.
Time frame: 2 years
Changes in circulating inflammatory cytokines and inflammatory response in circulating inflammatory cells associated with prednisolone and AZD4017 administration.
Time frame: 2 years
Changes in bone turnover associated with prednisolone and AZD4017 administration.
Time frame: 2 years
Changes in body composition (total and regional lean and fat mass) associated with prednisolone and AZD4017 administration.
Time frame: 2 years
Changes in urinary steroid metabolite profile associated with prednisolone and AZD4017 administration.
Time frame: 2 years

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2021.
Background: PubMed 10700481van Staa TP, Leufkens HG, Abenhaim L, Begaud B, Zhang B, Cooper C. Use of oral corticosteroids in the United Kingdom. QJM. 2000 Feb;93(2):105-11. doi: 10.1093/qjmed/93.2.105.
Background: PubMed 22807233Overman RA, Yeh JY, Deal CL. Prevalence of oral glucocorticoid usage in the United States: a general population perspective. Arthritis Care Res (Hoboken). 2013 Feb;65(2):294-8. doi: 10.1002/acr.21796.
Background: PubMed 23612224Gathercole LL, Lavery GG, Morgan SA, Cooper MS, Sinclair AJ, Tomlinson JW, Stewart PM. 11beta-Hydroxysteroid dehydrogenase 1: translational and therapeutic aspects. Endocr Rev. 2013 Aug;34(4):525-55. doi: 10.1210/er.2012-1050. Epub 2013 Apr 23.
Background: PubMed 24889609Morgan SA, McCabe EL, Gathercole LL, Hassan-Smith ZK, Larner DP, Bujalska IJ, Stewart PM, Tomlinson JW, Lavery GG. 11beta-HSD1 is the major regulator of the tissue-specific effects of circulating glucocorticoid excess. Proc Natl Acad Sci U S A. 2014 Jun 17;111(24):E2482-91. doi: 10.1073/pnas.1323681111. Epub 2014 Jun 2.
Background: PubMed 11788623Tomlinson JW, Draper N, Mackie J, Johnson AP, Holder G, Wood P, Stewart PM. Absence of Cushingoid phenotype in a patient with Cushing's disease due to defective cortisone to cortisol conversion. J Clin Endocrinol Metab. 2002 Jan;87(1):57-62. doi: 10.1210/jcem.87.1.8189.
Background: PubMed 22691057Scott JS, Bowker SS, Deschoolmeester J, Gerhardt S, Hargreaves D, Kilgour E, Lloyd A, Mayers RM, McCoull W, Newcombe NJ, Ogg D, Packer MJ, Rees A, Revill J, Schofield P, Selmi N, Swales JG, Whittamore PR. Discovery of a potent, selective, and orally bioavailable acidic 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitor: discovery of 2-[(3S)-1-[5-(cyclohexylcarbamoyl)-6-propylsulfanylpyridin-2-yl]-3-piperidyl]acetic acid (AZD4017). J Med Chem. 2012 Jun 28;55(12):5951-64. doi: 10.1021/jm300592r. Epub 2012 Jun 19.
Background: PubMed 23426618Hazlehurst JM, Gathercole LL, Nasiri M, Armstrong MJ, Borrows S, Yu J, Wagenmakers AJ, Stewart PM, Tomlinson JW. Glucocorticoids fail to cause insulin resistance in human subcutaneous adipose tissue in vivo. J Clin Endocrinol Metab. 2013 Apr;98(4):1631-40. doi: 10.1210/jc.2012-3523. Epub 2013 Feb 20.
Background: PubMed 23811853Tripathy D, Daniele G, Fiorentino TV, Perez-Cadena Z, Chavez-Velasquez A, Kamath S, Fanti P, Jenkinson C, Andreozzi F, Federici M, Gastaldelli A, Defronzo RA, Folli F. Pioglitazone improves glucose metabolism and modulates skeletal muscle TIMP-3-TACE dyad in type 2 diabetes mellitus: a randomised, double-blind, placebo-controlled, mechanistic study. Diabetologia. 2013 Oct;56(10):2153-63. doi: 10.1007/s00125-013-2976-z. Epub 2013 Jun 30.
Derived from this study: PubMed 37740611Gomez C, Alimajstorovic Z, Othonos N, Winter DV, White S, Lavery GG, Tomlinson JW, Sinclair AJ, Odermatt A. Identification of a human blood biomarker of pharmacological 11beta-hydroxysteroid dehydrogenase 1 inhibition. Br J Pharmacol. 2024 Mar;181(5):698-711. doi: 10.1111/bph.16251. Epub 2023 Oct 19.
Individual participant dataSharing planned: No

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.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AZD4017 and prednisolone in people with Iatrogenic Cushing's Disease, run by University of Oxford 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 13 inclusion and 16 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: finished, as of the sponsor's last update on 13 May 2021. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Changes in the detrimental side effects of prednisolone by AZD4017. (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03111810, which also lists 9 linked publications.

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 13 May 2021.