Clinical Trials Register

Summary
EudraCT Number:	2010-018285-23
Sponsor's Protocol Code Number:	18102009
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-06-07
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2010-018285-23

A.3

Full title of the trial

Effect of active vitamin D treatment on arterial stiffness and albuminuria in patients with type 2 diabetes and stage 3 chronic kidney disease

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Does vitamin D treatment have an effect on arterial stiffness and protein in urine in patients with type 2 diabetes and stage 3 chronic kidney disease

A.3.2

Name or abbreviated title of the trial where available

Vitamin D in Diabetes Trial (VDDT)

A.4.1

Sponsor's protocol code number

18102009

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	King's College London
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Diabetes UK
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	King's College London
B.5.2	Functional name of contact point	Diabetes Research
B.5.3	Address:
B.5.3.1	Street Address	3.11, FWB building, Stamford Street,
B.5.3.2	Town/ city	KCL Waterloo Campus, London
B.5.3.3	Post code	SE1 9NH
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	004402078484413
B.5.5	Fax number	00440207848456
B.Sponsor: 2
B.1.1	Name of Sponsor	Guy's and St.Thomas' NHS Foundation Trust
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Diabetes UK
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	King's College London
B.5.2	Functional name of contact point	Diabetes Reasearch
B.5.3	Address:
B.5.3.1	Street Address	Room 3.11, FWB building, Stamford Street, KCL Waterloo Campus
B.5.3.2	Town/ city	London
B.5.3.3	Post code	SE1 9NH
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	004402078484413
B.5.5	Fax number	004402078484567

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Rocaltrol
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Products Limited, 6 Falcon Way, Shire Park, Welwyn Garden City, AL7 1TW
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CALCITRIOL
D.3.9.1	CAS number	32222-06-3
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Diabetic kidney disease.

E.1.1.1

Medical condition in easily understood language

Kidney disease caused by diabetes

E.1.1.2

Therapeutic area

Body processes [G] - Physiological processes [G07]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10009119
E.1.2	Term	Chronic renal failure
E.1.2	System Organ Class	100000004857

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	PT
E.1.2	Classification code	10067585
E.1.2	Term	Type 2 diabetes mellitus
E.1.2	System Organ Class	10027433 - Metabolism and nutrition disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The main research question is to evaluate the effect of Calcitriol treatment as compared to placebo on arterial stiffness in patients with type 2 diabetes and chronic kidney disease. Arterial stiffness is a marker and predictor of cardiovascular disease risk. Arterial stiffness will be assessed by aortic pulse wave velocity (Ao-PWV) which is a measure of arterial stiffness. Ao-PWV measures the the speed of transmission of the pulse wave along the aorta the largest blood vessel in the body. The greater the speed the greater the arterial stiffness. Interventions that recuce arterial stiffness may prevent cardiovascular disease.
Currently it is not known if treatment with Calcitriol can affect arterial stiffness in patients with diabetes and kidney disease. We wish to study the effect of Calcitriol or placebo as add on treatment to existing medical treatments on arterial stiffness in a placebo controlled double blind study. Patients will continue with other medical treatments for their

E.2.2

Secondary objectives of the trial

Secondary research questions will be to evaluate the effect of Calcitriol treatment as compared to placebo on the amount of the protein albumin in the urine which is a marker of kidney disease and heart disease. Other secondary questions will be to compare the effect of calcitriol and placebo on augmentation index (a measurement of the pulse wave reflection on central pressures) measured at the wrist over the radial artery with a small pencil like probe. Similar to the Aortic pulse wave velocity measurements this is also non invasive. Other secondary endpoints questions include blood pressure, kidney function as measured by estimated glomerular filtration rate, changes in calcium and phosphate levels in the blood and hormones involved in regulating bone metabolism and blood pressure and quality of life as measured by a questionnaire.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

A sub study of the Vitamin D in Diabetes Trial (VDDT) to investigate the effects of active vitamin D on endothelial function in patients with type 2 diabetes and stage 3 chronic kidney disease

E.3

Principal inclusion criteria

1. Patients with a diagnosis of T2DM.
2. Patients aged between 40 and 75 years (inclusive).
3. Chronic Kidney disease (CKD) stage 3 [estimated glomerular filtration rate (eGFR*) 30-59 ml/min on the two most recent (within 12 months) consecutive measurements].
4. A history of an elevated urinary albumin excretion rate (UAER) [albumin: creatinine ratio≥ 2.5 mg/mmol in men and ≥3mg/mmol in women on more than three occasions or UAER ≥20mcg/min on at least two timed urine collections or two or more positive urine dipsticks results for proteinuria or two or more urine protein creatinine ratios (PCR)>15 mg/mmol] or clinical evidence of diabetic nephropathy
5. Normal corrected serum calcium (2.1-2.6mmol/l).
6. Normal phosphate (0.8-1.5 mmol/l) levels.
7. A raised intact parathyroid hormone (iPTH) level between 30 pg/ml and 200pg/ml at screening visit or a history of a raised intact parathyroid hormone (iPTH) level between 30 pg/ml and 200pg/ml in the 3 months preceding screening visit.
8. Written informed consent to participate in the study prior to any study procedures.
9. Ability to communicate and comply with all study requirements.

E.4

Principal exclusion criteria

• An iPTH ≥200 pg/ml at study entry (a conservative treatment threshold for initiating active vitamin D treatment for prevention of renal osteodystrophy).
• History of non diabetic or obstructive kidney disease.
• Poorly controlled hypertension (systolic and diastolic blood pressure >180mmHg and >110 mmHg respectively).
• Presence of connective tissue diseases known to affect arterial vasculature.
• Atrial fibrillation or other cardiac rhythm disorders.
• Pregnancy or lactation.
• History of a cardiovascular or cerebrovascular event in the preceding 6 months.
• Patients already on vitamin D (inactive or active) treatment.

E.5 End points

E.5.1

Primary end point(s)

The primary end point will be change from baseline in Ao-PWV. The primary population used in this assessment will be the intention to treat population.
The primary population used in these assessments will be the intention to treat population.

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline is defined as visit 3. Endpoint will be defined as the last available post-baseline measurement of Ao-PWV (up to and including visit 7).

E.5.2

Secondary end point(s)

Secondary endpoints will be change from baseline in; UAER, augmentation index, brachial and central systolic and diastolic blood pressure, progression to clinical indication for vitamin D replacement or iPTH≥200 pg/ml, eGFR, serum calcium and phosphate levels, alkaline phosphate levels, urine calcium excretion, quality of life, number of hypercalcaemic events requiring withdrawal from study, hsCRP, iPTH, plasma renin activity and active vitamin D levels.Flow mediated dilatation, cardiac autonomic tests are exploratory secondary endpoints and will also be reported along with the above endpoints in final clinical study report (CSR)

E.5.2.1

Timepoint(s) of evaluation of this end point

All trial visits

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

both groups receive open label placebo for 12 weeks after 48 weeks treatment with active/placebo

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of the study is defined as the date on which the last participant completes the last visit (includes follow−up visit).

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

150

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

150

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

150

F.4.2

For a multinational trial

F.4.2.1

In the EEA

150

F.4.2.2

In the whole clinical trial

150

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Standard routine care

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2010-06-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-04-29

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-04-01

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