Post-Transplant Glucocorticoid Induced DiabetesPhase 4PTHGNCT01648218

Insulin Therapy for Post-transplant Glucocorticoid Induced Hyperglycemia

A Phase 4 study testing Neutral protamine hagedorn (NPH) insulin, Regular human insulin or Insulin Aspart and Insulin glargine in people with Post-Transplant Glucocorticoid Induced Diabetes, run by Vancouver General Hospital at 1 site in Canada.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Post-Transplant Glucocorticoid Induced Diabetes
What is being tested?: Neutral protamine hagedorn (NPH) insulin, Regular human insulin or Insulin Aspart and Insulin glargine
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 5 participants
Where: 1 siteCanada
Study dates: Aug 2012to Jun 2013
Phase: Phase 4
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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Have undergone bone marrow, liver, lung, or renal transplant.
Be using once daily oral glucocorticoid therapy (total daily dose of Prednisone ≥10 mg, Hydrocortisone ≥40 mg, Dexamethasone ≥1.5 mg) administered in the morning and expected to continue for at least 2 weeks.
Have pre-existing or newly diagnosed diabetes mellitus established by any of the criteria listed below:
Fasting plasma glucose ≥7.0 mmol/L (repeated x 1)
Any plasma glucose ≥11.0 mmol/L
Have at least three pre-meal inpatient capillary blood glucose (CBG) readings ≥ 7.8 mmol/L
Be eating meals by mouth

Who cannot join

Heart, Pancreas, Islet cell transplant recipients
Previous use of Basal-Bolus or Pre-Mixed Insulin regimen
Diabetes mellitus type I
NPO (not eating meals by mouth)
Receiving enteral (tube feeds) or parenteral (TPN) nutrition

Trial locations and contacts

1 site in 1 country.

Canada1 site

Vancouver General Hospital - Jim Pattison Pavilion
Vancouver, British Columbia, V5Z 1M9

Other trials in Canada

About this study

No consensus guidelines exist for management of post-transplant glucocorticoid induced hyperglycemia, but most published reviews recommend insulin as first line therapy. A variety of insulin regimens have been proposed, including mealtime short-acting regular or analog insulin, once daily neutral protamine hagedorn (NPH) insulin, pre-mixed insulin, or basal insulin alone such as glargine or detemir. However, no randomized trial has ever examined different insulin regimens to determine which most effectively controls post-transplant steroid-induced hyperglycemia. Consequently, the proposed study intends to examine three commonly used insulin regimens used for managing post-transplant once-daily glucocorticoid-induced hyperglycemia to determine which is most effective:

Group 1: Intermediate-acting (NPH) insulin at breakfast
Group 2: Short-acting insulin (regular or aspart) before meals
Group 3: Insulin glargine at breakfast

Question/Hypothesis:

Among three commonly used insulin regimens, which is most effective for managing post-transplant once-daily glucocorticoid-induced hyperglycemia?

Conditions: Post-Transplant Glucocorticoid Induced Diabetes
Being tested: Neutral protamine hagedorn (NPH) insulin, Regular human insulin or Insulin Aspart, Insulin glargine
Keywords: glucocorticoid, diabetes mellitus, post-transplant, insulin
Medical subject headings: Diabetes Mellitus, Insulin Resistance

What participants receive

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

Neutral protamine hagedorn (NPH) insulinDrug
Also called Humulin N, Novolin N
Regular human insulin or Insulin AspartDrug
Also called Humulin R, Novolin R, Novolog, NovoRapid
Insulin glargineDrug
Also called Lantus

Study groups in NCT01648218
Study group	Role	What they receive
Neutral protamine hagedorn (NPH) insulin	Active comparator	Drug: Neutral protamine hagedorn (NPH) insulin Other Names: Humulin N, Novolin N Route: Subcutaneous; Dosage: No fixed dose, varies between subjects; Frequency: daily before breakfast; Duration: 12 hours; for duration subjects are concurrently administered once-daily glucocorticoid. Receives: Drug: Neutral protamine hagedorn (NPH) insulin
Regular or Aspart insulin	Experimental	Drug: Regular human insulin or Insulin Aspart Other Names: Humulin R, Novolin R, Novolog, NovoRapid Route: Subcutaneous; Dosage: No fixed dose, varies between subjects; Frequency: daily before meals; Duration: 2 hours (Aspart) or 6 hours (Regular); for duration subjects are concurrently administered once-daily glucocorticoid. Receives: Drug: Regular human insulin or Insulin Aspart
Insulin glargine	Experimental	Drug: Insulin glargine Other Names: Lantus Route: Subcutaneous; Dosage: No fixed dose, varies between subjects; Frequency: daily before breakfast; Duration: 24 hours; for duration subjects are concurrently administered once-daily glucocorticoid. Receives: Drug: Insulin glargine

What is being measured

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

Blood glucose - inpatient
Mean time from baseline to achieve at least 80% of pre-meal capillary blood glucose values within 5.0 - 7.8 mmol/L over a 48 hour period during hospitalization
Measured: Time (days) from enrollment to described treatment range, an expected average of 7 days

Secondary outcomes (13)

Blood glucose - inpatient
Mean inpatient capillary blood glucose (mmol/L) from enrollment to discharge from hospital
Measured: Subjects will be followed from enrollment for the remainder of hospital stay (days), an expected average of 21 days
Post prandial blood glucose - inpatient
Mean inpatient two-hour post-lunch capillary blood glucose (mmol/L) from enrollment to discharge from hospital
Measured: Subjects will be followed from enrollment for the remainder of hospital stay (days), an expected average of 21 days
Length of inpatient hospital stay
Length of stay in hospital (days) from enrollment to discharge from hospital
Measured: Subjects will be followed from enrollment for the remainder of hospital stay (days), an expected average of 21 days
Blood glucose
Mean fasting blood glucose (mmol/L) from enrollment to 3 months
Measured: Enrollment to 3 months
Hemoglobin A1C
Mean hemoglobin A1C (%) from enrollment to 3 months
Measured: Enrollment to 3 months
Post prandial blood glucose
Mean two-hour post-lunch capillary blood glucose (mmol/L) from enrollment to 3 months
Measured: Enrollment to 3 months
Hypoglycemic episodes
Hypoglycemic episodes defined as:
(1) Mild - any measured CBG 3.0-4.0 mmol/L; (2) Severe - any episode of hypoglycemia with a measured CBG < 3.0 mmol/L, OR which the subject is not able to recognize and treat without the direct (substantial) intervention of a professional caregiver, nurse or physician (e.g. intravenous dextrose or intramuscular glucagon)
Measured: Enrollment to 3 months
Glycemic treatment failure
Hypoglycemic treatment failure: subject experiences ≥3 hypoglycemic episodes (≤ 4.0 mmol/L) over any 5 day period or a single severe hypoglycemic event (as previously defined), they will be withdrawn from study and managed at discretion of attending physician, or hospital endocrine consult service.
Hyperglycemic treatment failure: Severe hyperglycemia defined as CBG >20 mmol/L. If subject experiences ≥3 severe hyperglycemic measures over the course of 48 hours they will be withdrawn from the study and managed at discretion of attending physician, or hospital endocrine consult service.
Measured: Enrollment to 3 months
Cardiovascular events
New cardiovascular events defined as: myocardial infarction, new or worsened congestive heart failure, stroke, and cardiac arrhythmia.
Measured: Enrollment to 3 months
Post-transplant infections or new antibiotic use
Post-transplant infections or new antibiotic use from enrollment to 3 months.
Measured: Enrollment to 3 months
Transplant graft failure
Transplant graft failure (as specified by subject's medical transplant physician) from enrollment to 3 months.
Measured: Enrollment to 3 months
New acute renal failure
New acute renal failure is defined according to Acute Kidney Network Guidelines: rapid time course and decreased kidney function according to an absolute Creatinine (Cr) rise greater than 26 μmol/L, greater than 2-fold increase in serum Cr from baseline, or urine output less than 0.5 mL/kg/hr for greater than 6 hours
Measured: Enrollment to 3 months
Mortality
Overall subject mortality from baseline to 3 months.
Measured: Enrollment to 3 months

Timeline

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

Aug 2012Jun 2013

First posted24 Jul 2012 (estimated)
Study startAug 2012
Primary completionApr 2013
Study completionJun 2013

Why it stopped: Poor enrollment

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (5)Papers the sponsor has linked to this study.
Other trials for Post-Transplant Glucocorticoid Induced DiabetesStudies 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 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 5 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01648218
Sponsor's protocol ID: PTHG.VGH.UBC
Acronym: PTHG
Status last verified: Dec 2015
First submitted: 12 Jul 2012
Last updated: 9 Dec 2015
Results posted: No
Data monitoring committee: No

Publications

Lane JT, Dagogo-Jack S. Approach to the patient with new-onset diabetes after transplant (NODAT). J Clin Endocrinol Metab. 2011 Nov;96(11):3289-97. doi: 10.1210/jc.2011-0657.
PubMed 22058376
Sarno G, Muscogiuri G, De Rosa P. New-onset diabetes after kidney transplantation: prevalence, risk factors, and management. Transplantation. 2012 Jun 27;93(12):1189-95. doi: 10.1097/TP.0b013e31824db97d.
PubMed 22475764
Griffith ML, Jagasia M, Jagasia SM. Diabetes mellitus after hematopoietic stem cell transplantation. Endocr Pract. 2010 Jul-Aug;16(4):699-706. doi: 10.4158/EP10027.RA.
PubMed 20439241
Lansang MC, Hustak LK. Glucocorticoid-induced diabetes and adrenal suppression: how to detect and manage them. Cleve Clin J Med. 2011 Nov;78(11):748-56. doi: 10.3949/ccjm.78a.10180.
PubMed 22049542
Umpierrez GE, Hellman R, Korytkowski MT, Kosiborod M, Maynard GA, Montori VM, Seley JJ, Van den Berghe G; Endocrine Society. Management of hyperglycemia in hospitalized patients in non-critical care setting: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2012 Jan;97(1):16-38. doi: 10.1210/jc.2011-2098.
PubMed 22223765

Study at a glance

From the registry record, last updated by the sponsor on 9 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Insulin Therapy for Post-transplant Glucocorticoid Induced Hyperglycemia
ClinicalTrials.gov ID: NCT01648218
Acronym / sponsor ID: PTHG / PTHG.VGH.UBC
Conditions: Post-Transplant Glucocorticoid Induced Diabetes
Keywords: glucocorticoid, diabetes mellitus, post-transplant, insulin
Phase: Phase 4
Study type: Interventional
Recruitment status: TerminatedReason stopped: Poor enrollment
Enrolment: 5 participants (actual)
Lead sponsor: Vancouver General HospitalUniversity, hospital or other
Study start: Aug 2012
Primary completion: Apr 2013 (actual)
Study completion: Jun 2013 (actual)
First posted: 24 Jul 2012 (estimated)
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.

Group 1: Intermediate-acting (NPH) insulin at breakfast
Group 2: Short-acting insulin (regular or aspart) before meals
Group 3: Insulin glargine at breakfast

Question/Hypothesis:

Among three commonly used insulin regimens, which is most effective for managing post-transplant once-daily glucocorticoid-induced hyperglycemia?

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Neutral protamine hagedorn (NPH) insulin	Active comparator	Drug: Neutral protamine hagedorn (NPH) insulinDrug: Neutral protamine hagedorn (NPH) insulin Other Names: Humulin N, Novolin N Route: Subcutaneous; Dosage: No fixed dose, varies between subjects; Frequency: daily before breakfast; Duration: 12 hours; for duration subjects are concurrently administered once-daily glucocorticoid.
Regular or Aspart insulin	Experimental	Drug: Regular human insulin or Insulin AspartDrug: Regular human insulin or Insulin Aspart Other Names: Humulin R, Novolin R, Novolog, NovoRapid Route: Subcutaneous; Dosage: No fixed dose, varies between subjects; Frequency: daily before meals; Duration: 2 hours (Aspart) or 6 hours (Regular); for duration subjects are concurrently administered once-daily glucocorticoid.
Insulin glargine	Experimental	Drug: Insulin glargineDrug: Insulin glargine Other Names: Lantus Route: Subcutaneous; Dosage: No fixed dose, varies between subjects; Frequency: daily before breakfast; Duration: 24 hours; for duration subjects are concurrently administered once-daily glucocorticoid.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Have undergone bone marrow, liver, lung, or renal transplant.
Be using once daily oral glucocorticoid therapy (total daily dose of Prednisone ≥10 mg, Hydrocortisone ≥40 mg, Dexamethasone ≥1.5 mg) administered in the morning and expected to continue for at least 2 weeks.
Have pre-existing or newly diagnosed diabetes mellitus established by any of the criteria listed below:
Have at least three pre-meal inpatient capillary blood glucose (CBG) readings ≥ 7.8 mmol/L
Be eating meals by mouth

Key exclusion criteria (5 listed)

Heart, Pancreas, Islet cell transplant recipients
Previous use of Basal-Bolus or Pre-Mixed Insulin regimen
Diabetes mellitus type I
NPO (not eating meals by mouth)
Receiving enteral (tube feeds) or parenteral (TPN) nutrition

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
Neutral protamine hagedorn (NPH) insulinAlso: Humulin N, Novolin N	Drug	Neutral protamine hagedorn (NPH) insulin
Regular human insulin or Insulin AspartAlso: Humulin R, Novolin R, Novolog, NovoRapid	Drug	Regular or Aspart insulin
Insulin glargineAlso: Lantus	Drug	Insulin glargine

Primary outcome

Blood glucose - inpatient
Time frame: Time (days) from enrollment to described treatment range, an expected average of 7 days
Mean time from baseline to achieve at least 80% of pre-meal capillary blood glucose values within 5.0 - 7.8 mmol/L over a 48 hour period during hospitalization

13 secondary outcomes

Blood glucose - inpatient
Time frame: Subjects will be followed from enrollment for the remainder of hospital stay (days), an expected average of 21 days
Post prandial blood glucose - inpatient
Time frame: Subjects will be followed from enrollment for the remainder of hospital stay (days), an expected average of 21 days
Length of inpatient hospital stay
Time frame: Subjects will be followed from enrollment for the remainder of hospital stay (days), an expected average of 21 days
Blood glucose
Time frame: Enrollment to 3 months
Hemoglobin A1C
Time frame: Enrollment to 3 months
Post prandial blood glucose
Time frame: Enrollment to 3 months
Hypoglycemic episodes
Time frame: Enrollment to 3 months
Glycemic treatment failure
Time frame: Enrollment to 3 months
Cardiovascular events
Time frame: Enrollment to 3 months
Post-transplant infections or new antibiotic use
Time frame: Enrollment to 3 months
Transplant graft failure
Time frame: Enrollment to 3 months
New acute renal failure
Time frame: Enrollment to 3 months
Mortality
Time frame: Enrollment to 3 months

Results and safety

The study was stopped early (reason given: Poor enrollment). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2015.
Background: PubMed 22058376Lane JT, Dagogo-Jack S. Approach to the patient with new-onset diabetes after transplant (NODAT). J Clin Endocrinol Metab. 2011 Nov;96(11):3289-97. doi: 10.1210/jc.2011-0657.
Background: PubMed 22475764Sarno G, Muscogiuri G, De Rosa P. New-onset diabetes after kidney transplantation: prevalence, risk factors, and management. Transplantation. 2012 Jun 27;93(12):1189-95. doi: 10.1097/TP.0b013e31824db97d.
Background: PubMed 20439241Griffith ML, Jagasia M, Jagasia SM. Diabetes mellitus after hematopoietic stem cell transplantation. Endocr Pract. 2010 Jul-Aug;16(4):699-706. doi: 10.4158/EP10027.RA.
Background: PubMed 22049542Lansang MC, Hustak LK. Glucocorticoid-induced diabetes and adrenal suppression: how to detect and manage them. Cleve Clin J Med. 2011 Nov;78(11):748-56. doi: 10.3949/ccjm.78a.10180.
Background: PubMed 22223765Umpierrez GE, Hellman R, Korytkowski MT, Kosiborod M, Maynard GA, Montori VM, Seley JJ, Van den Berghe G; Endocrine Society. Management of hyperglycemia in hospitalized patients in non-critical care setting: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2012 Jan;97(1):16-38. doi: 10.1210/jc.2011-2098.
Multilingual dietary instructions to be distributed to ALL subjects during study from the Canadian Diabetes AssociationLink provided by the sponsor.

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.

Breay W Paty, MD, FRCPC principal investigator

Vancouver General Hospital, University of British Columbia

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

Questions about this trial

What is this clinical trial studying?

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 7 inclusion and 5 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: stopped early, as of the sponsor's last update on 9 Dec 2015. 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 Canada. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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 was stopped early (reason given: Poor enrollment). 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?

Blood glucose - inpatient (time frame: Time (days) from enrollment to described treatment range, an expected average of 7 days). 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 NCT01648218, which also lists 5 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 9 Dec 2015.