Clinical Trials Register

Summary
EudraCT Number:	2014-000047-33
Sponsor's Protocol Code Number:	VitD-EX1.0
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2014-02-24
Trial 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

Netherlands - Competent Authority

A.2

EudraCT number

2014-000047-33

A.3

Full title of the trial

The effect of high-resistance muscle strength training and vitamin D
supplementation in persons with knee osteoarthritis

Het effect van hoog-intensieve spierkrachttraining en vitamine D suppletie
bij mensen met knieartrose

A.3.1

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

The effect of intensive muscle strength training and vitamin D supplements
in persons with knee osteoarthritis

Het effect van intensieve spierkrachttraining en extra vitamine D suppletie
bij mensen met knieartrose

A.3.2

Name or abbreviated title of the trial where available

vitD-EX

A.4.1

Sponsor's protocol code number

VitD-EX1.0

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	VU University Medical Centre
B.1.3.4	Country	Netherlands
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	Reumafonds
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Reade
B.5.2	Functional name of contact point	Trial coordinator
B.5.3	Address:
B.5.3.1	Street Address	dr. Jan van Breemenstraat
B.5.3.2	Town/ city	Amsterdam
B.5.3.3	Post code	1056AB
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	0031(0)205896291
B.5.5	Fax number	0031(0)205896316
B.5.6	E-mail	m.vd.leeden@reade.nl

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	Devaron
D.2.1.1.2	Name of the Marketing Authorisation holder	Vemedia Manufacturing BV
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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.3.1	Product name	Devaron
D.3.2	Product code	Vitamin D
D.3.4	Pharmaceutical form	Tablet
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	Colecalciferol
D.3.9.1	CAS number	67-97-0
D.3.9.2	Current sponsor code	Vitamin D
D.3.9.3	Other descriptive name	COLECALCIFEROL
D.3.9.4	EV Substance Code	SUB06794MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1200
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	Yes
D.3.11.13.1	Other medicinal product type	vitamin

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	Tablet
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

knee osteoarthritis
vitamin D deficiency

knieartrose
vitamine D deficientie

E.1.1.1

Medical condition in easily understood language

cartilage wear of knee joint
low vitamin D level

kraakbeenschade aan het kniegewricht
laag vitamine D gehalte

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To determine (1) whether high-resistance strength training (70-80% of one-repetition maximum (1RM)) is more effective in improving muscle strength compared to low-resistance strength training (20-30% of 1RM) and (2) whether vitamin D supplementation enhances the effect of muscle strength training on muscle strength in knee OA patients with vitamin D deficiency.
The ultimate goal of the intervention study is to optimize strength training in knee OA, thereby increasing the beneficial effect on pain and activity limitations.

(1) Bepalen of hoog-intensieve krachttraining (op 70-80% van het maximum) effectiever is om spierkracht te verbeteren dan laag-intensieve krachttraining (op 20-30% van het maximum).
(2) Bepalen of vitamine D supplementen het effect van spierkrachttraining op spierkracht versterken.
Het uiteindelijke doel van deze interventiestudie is het optimaliseren van de effecten van spierkrachttraining voor patiënten met knieartrose.

E.2.2

Secondary objectives of the trial

To determine (1) whether high-resistance strength training (70-80% of one-repetition maximum (1RM)) is more effective in improving knee pain, activity limitations, inflammatory markers, falls and fractures, self-reported knee instability and depressive and anxious mood compared to low-resistance strength training (20-30% of 1RM) and (2) whether vitamin D supplementation enhances the effect of muscle strength training on knee pain, activity limitations, inflammatory markers, falls and fractures, self-reported knee instability and depressive and anxious mood.

(1) Bepalen of hoog-intensieve krachttraining (op 70-80% van het maximum) effectiever is om kniepijn, beperkingen in activiteiten, ontstekingsmarkers, vallen en fracturen, zelfgerapporteerde knie-instabiliteit en depressieve en angstige gevoelens te verbeteren dan laag-intensieve krachttraining (op 20-30% van het maximum).
(2) Bepalen of vitamine D supplementen het effect van spierkrachttraining versterken op: kniepijn, beperkingen in activiteiten, ontstekingsmarkers, vallen en fracturen, zelfgerapporteerde knie-instabiliteit en depressieve en angstige gevoelens.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Knee pain and at least 2 of the following 5 items: morning stiffness < 30 minutes, crepitations, bone sensitivity, bony enlargement of the joint margin, no palpable warmth
- Age ≥ 55 and ≤ 80 years
- Vitamin D deficiency: 25(OH)D level >15nmol/L and <50 nmol/L (in winter) or <70nmol/L (in summer)

- kniepijn en tenminste 2 van de volgende 5 items: ochtendstijfheid , 30 minuten, crepitaties, bontgevoeligheid, botvergroting van de rand van de gewrichtsspleet, geen palpabele warmte
- leeftijd ≥55 en ≤80 jaar
- vitamine D deficiëntie: 25(OH)D niveau >15nmol/L en <50nmol/L (in de winter) of <70nmol/L (in de zomer)

E.4

Principal exclusion criteria

- Other forms of arthritis than OA
- Absolute contra-indication for exercise therapy/strength training
- Inability to perform strength training program due to severe co-morbidity
- Use of vitamin D supplements >400 IU daily
- Living in a nursing home
-

- andere vormen van artritis dan atrose
- absolute contra-indicatie voor oefentherapie/krachttraining
- ernstige comorbiditeit
- gebruik van vitamine D supplementen >400 ie dagelijks
- woonachtig in een verzorging- of verpleeghuis

E.5 End points

E.5.1

Primary end point(s)

change in (isokinetic) muscle strength of quadriceps en hamstrings muscles

verandering in (isokinetische) spierkracht van quadriceps en hamstrings

E.5.1.1

Timepoint(s) of evaluation of this end point

6 and 12 months

6 en 12 maanden

E.5.2

Secondary end point(s)

Change in: knee pain, activity limitations (self-report and performance based), inflammatory markers (i.e. C-reactive protein and Erythrocyte Sedimentation Rate), falls and fractures, self-reported knee instability, depression and anxiety. Global perceived effect.

Verandering in: kniepijn, beperkingen in activiteiten, inflammatiemarkers, vallen en fracturen, zelfgerapporteerde knie-instabiliteit en depressie en angst. Zelf ervaren herstel

E.5.2.1

Timepoint(s) of evaluation of this end point

6 and 12 months

6 en 12 maanden

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)

Yes

E.7.4

Therapeutic use (Phase IV)

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

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

vitamin D versus placebo: double blind, high versus low resistance training: single blind

2x2 factorial design in 220 patients with knee OA and vitamin D deficiency

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

Yes

E.8.4

The trial involves multiple sites in the 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

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

LVLS

laatste meting van laatste proefpersoon

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

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:

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

220

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)

None

Geen

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

2014-02-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-03-20

P. End of Trial
P.	End of Trial Status	Ongoing

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