Vitamin D DeficiencyNCT03420378
Central Sensitization in Vitamin D Deficiency
A study testing vitamin D in people with Vitamin D Deficiency and Central Sensitisation, run by Marmara University at 1 site in Turkey (Türkiye).
Trial summary
The purpose of this study is to investigate the presence of central sensitization in vitamin D deficiency and its effect on cutaneous silent period, pain, and quality of life. The secondary purpose of the study is to investigate whether a change in cutaneous silent period parameters, pain severity and neuropathic… Read more about this study
- Who is it for?
- Ages 18 to 65 years, women only
- Conditions the study is for
- Vitamin D Deficiency, Central Sensitisation
- What is being tested?
- vitamin D
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 28 Jan 2018to 19 Dec 2018
- Phase
- Interventional
- 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 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Presence of widespread pain
- Presence of vitamin D deficit
Who cannot join
- Any contraindication of performing silent cutaneous period
- Any contraindication for vitamin d use
- Presence of conditions that affect cutaneous silent period like the presence of carpal tunnel syndrome and polyneuropathies
- Defective peripheric autonomic nervous system findings
- Not being able to write and read
- Not being able to communicate
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Central Sensitization in Vitamin D Deficiency and Effect of Vitamin D Replacement on Cutaneous Silent Period
The purpose of this study is to investigate the presence of central sensitization in vitamin D deficiency and its effect on cutaneous silent period, pain, and quality of life. The secondary purpose of the study is to investigate whether a change in cutaneous silent period parameters, pain severity and neuropathic sensitization and quality of life after vitamin D replacement.
Read the detailed description
Vitamin D deficiency is a pandemia. Main causes of this is insufficient exposure to sunlight. Vitamin D deficiency is related to conditions like various cancers, autoimmune diseases, hypertension and growth retardation in children (1).
International Association for the study of pain has defined pain as "An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage." (2). Pain lasting longer than 3 months has been deemed as chronic pain (3). Vitamin D deficiency influences various types of pain, including chronic pain (4,5,6,7).
Vitamin D influences the musculoskeletal system via the calcium-phosphorus metabolism and the receptors found in skeletal muscle cells (8). Vitamin D deficiency has been shown to decrease muscle strength, the this decrease in proximal muscles affect postural stability and can increase falls. Vitamin D deficiency also causes problems in bone mineralization, causing isolated or widespread pain in muscles, bones and joints. These patients end up getting wrong diagnoses such as fibromyalgia, osteoarthritis, inflammatory arthritis, and chronic fatigue syndrome (1,7). Vitamin D deficiency causes hyperinnervation and hypersensitivity on nerves and cause pain to be felt more intensely (5).
In a normal skeletal muscle, during an isometric contraction, a number of motor unit will be activated. These motor units produce a stable electromyography pattern and keep their own frequencies during contraction. If the nerve, tendon or a cutaneous nerve nearby is stimulated, electromyographic activity is disrupted and a bioelectric silence occurs. This is called cutaneous silent period (CSP). It is an inhibitory spinal reflex and its afferents consist of A-delta nerve fibers.
In various studies, CSP has been shown to be clinically beneficial in conditions like peripheral neuropathy, syringomyelia, Parkinson's disease, restless leg syndrome and fibromyalgia.
von Känel R et al. has investigated the effect of vitamin D deficiency on widespread pain index (WPI) and symptom severity score (SSS) and found out that it increases central sensitivity (8). In thei study, thy did not utilize any electrophysiologic objective measurements. Akyüz et al. have investigated the effect of vitamin D deficiency on chronic pain and nerve conduction studies; they have shown that vitamin D is correlated with various nerve conduction parameters while these parameters do not change after replacement (9,10).
Patients with vitamin D deficiency and healthy controls with normal vitamin D levels will be compared in terms of cutaneous silent period parameters, pain severity and neuropathic sensitization and quality of life. Cutaneous silent period parameters (duration and latency ), The Leeds Assessment of Neuropathic Symptoms \& Signs and Nottingham Health Profile will be used for the assessments. Patients with vitamin D deficiency will receive vitamin D supplementation therapy. Before and after therapy, cutaneous silent period parameters, LANSS scores and Nottingham Health Profile will measured before and 8 weeks after starting vitamin D supplementation therapy.
- Conditions
- Vitamin D Deficiency, Central Sensitisation
- Being tested
- vitamin D
- Keywords
- Central Sensitisation, Cutaneous Silent Period, Vitamin D Deficiency
- Medical subject headings
- Vitamin D Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
vitamin DDietary supplement
Vitamin D replacement
| Study group | Role | What they receive |
|---|---|---|
| Interventional Arm | Experimental | Patients with vitamin D deficiency will receive vitamin D replacement therapy. Before and after therapy, cutaneous silent period will be measured from each upper extremity and latencies will be recorded. Their LANSS scores and Notthingham Health Profile will be recorded before and after treatment. Receives: Dietary Supplement: vitamin D |
What is being measured
The primary outcome is the main question the study is designed to answer.
cutaneous silent period latency (ms)
the brief interruption in voluntary contraction that follows strong electrical stimulation (painful) of a cutaneous nerve
Measured: 8 weeks
cutaneous silent period duration (ms)
the brief interruption in voluntary contraction that follows strong electrical stimulation (painful) of a cutaneous nerve
Measured: 8 weeks
Secondary outcomes (3)
Visual analog scale (VAS) of pain
line from 0: no pain to 10:worst pain
Measured: 8 weeks
Leeds assessment of neuropathic symptoms and signs (LANSS)
Reduction of pain related to central sensitization. LANSS scale ⩾ 12 refers to "Neu- neuropathic sensitization"
Measured: 8 weeks
The Nottingham Health Profile (NHP)
The Nottingham Health Profile is intended for primary health care, to provide a brief indication of a patient's perceived emotional, social and physical health problems. The number of questions answered "yes" in each subgroup is divided by the total number of questions in the same subgroup and the result is multiplied by 100. Each subgroup has a value of between 0 and 100, with 100 points being considered the best general QoL for the calculated subgroup and 0 points being considered as the worst QoL for the same subgroup.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2018
- Study start28 Jan 2018
- Primary completion19 Dec 2018
- Study completion19 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Vitamin D DeficiencyStudies 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 N/A
- Primary purpose
- Screening
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Marmara University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ozge Kenis Coskun, MD, Principal investigator, Marmara University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03420378
- Sponsor's protocol ID
- 12.2017.123
- Status last verified
- Dec 2018
- First submitted
- 28 Jan 2018
- Last updated
- 20 Dec 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004 Mar;79(3):362-71. doi: 10.1093/ajcn/79.3.362.
PubMed 14985208Hamilton B. Vitamin D and human skeletal muscle. Scand J Med Sci Sports. 2010 Apr;20(2):182-90. doi: 10.1111/j.1600-0838.2009.01016.x. Epub 2009 Oct 5.
PubMed 19807897Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM; Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Jul;96(7):1911-30. doi: 10.1210/jc.2011-0385. Epub 2011 Jun 6.
PubMed 21646368Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008 Apr;87(4):1080S-6S. doi: 10.1093/ajcn/87.4.1080S.
PubMed 18400738Breivik H, Collett B, Ventafridda V, Cohen R, Gallacher D. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain. 2006 May;10(4):287-333. doi: 10.1016/j.ejpain.2005.06.009. Epub 2005 Aug 10.
PubMed 16095934Lotfi A, Abdel-Nasser AM, Hamdy A, Omran AA, El-Rehany MA. Hypovitaminosis D in female patients with chronic low back pain. Clin Rheumatol. 2007 Nov;26(11):1895-901. doi: 10.1007/s10067-007-0603-4. Epub 2007 Mar 22.
PubMed 17377737Wicherts IS, van Schoor NM, Boeke AJ, Visser M, Deeg DJ, Smit J, Knol DL, Lips P. Vitamin D status predicts physical performance and its decline in older persons. J Clin Endocrinol Metab. 2007 Jun;92(6):2058-65. doi: 10.1210/jc.2006-1525. Epub 2007 Mar 6.
PubMed 17341569Mascarenhas R, Mobarhan S. Hypovitaminosis D-induced pain. Nutr Rev. 2004 Sep;62(9):354-9. doi: 10.1111/j.1753-4887.2004.tb00061.x.
PubMed 15497769Gloth FM 3rd, Lindsay JM, Zelesnick LB, Greenough WB 3rd. Can vitamin D deficiency produce an unusual pain syndrome? Arch Intern Med. 1991 Aug;151(8):1662-4.
PubMed 1872673Haroon M, FitzGerald O. Vitamin D deficiency: subclinical and clinical consequences on musculoskeletal health. Curr Rheumatol Rep. 2012 Jun;14(3):286-93. doi: 10.1007/s11926-012-0244-8.
PubMed 22328176Tague SE, Clarke GL, Winter MK, McCarson KE, Wright DE, Smith PG. Vitamin D deficiency promotes skeletal muscle hypersensitivity and sensory hyperinnervation. J Neurosci. 2011 Sep 28;31(39):13728-38. doi: 10.1523/JNEUROSCI.3637-11.2011.
PubMed 21957236von Kanel R, Muller-Hartmannsgruber V, Kokinogenis G, Egloff N. Vitamin D and central hypersensitivity in patients with chronic pain. Pain Med. 2014 Sep;15(9):1609-18. doi: 10.1111/pme.12454. Epub 2014 Apr 14.
PubMed 24730754Kuru P, Akyuz G, Yagci I, Giray E. Hypovitaminosis D in widespread pain: its effect on pain perception, quality of life and nerve conduction studies. Rheumatol Int. 2015 Feb;35(2):315-22. doi: 10.1007/s00296-014-3099-7. Epub 2014 Aug 2.
PubMed 25085713Akyuz G, Sanal-Toprak C, Yagci I, Giray E, Kuru-Bektasoglu P. The effect of vitamin D supplementation on pain, quality of life, and nerve conduction studies in women with chronic widespread pain. Int J Rehabil Res. 2017 Mar;40(1):76-83. doi: 10.1097/MRR.0000000000000211.
PubMed 28030514
Study at a glance
From the registry record, last updated by the sponsor on 20 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Central Sensitization in Vitamin D Deficiency and Effect of Vitamin D Replacement on Cutaneous Silent Period
- ClinicalTrials.gov ID
- NCT03420378
- Acronym / sponsor ID
- 12.2017.123
- Conditions
- Vitamin D Deficiency, Central Sensitisation
- Keywords
- Central Sensitisation, Cutaneous Silent Period, Vitamin D Deficiency
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Marmara UniversityUniversity, hospital or other
- Study start
- 28 Jan 2018 (actual)
- Primary completion
- 19 Dec 2018 (actual)
- Study completion
- 19 Dec 2018 (actual)
- First posted
- 5 Feb 2018 (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.
The purpose of this study is to investigate the presence of central sensitization in vitamin D deficiency and its effect on cutaneous silent period, pain, and quality of life. The secondary purpose of the study is to investigate whether a change in cutaneous silent period parameters, pain severity and neuropathic sensitization and quality of life after vitamin D replacement.
Detailed description
Vitamin D deficiency is a pandemia. Main causes of this is insufficient exposure to sunlight. Vitamin D deficiency is related to conditions like various cancers, autoimmune diseases, hypertension and growth retardation in children (1).
International Association for the study of pain has defined pain as "An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage." (2). Pain lasting longer than 3 months has been deemed as chronic pain (3). Vitamin D deficiency influences various types of pain, including chronic pain (4,5,6,7).
Vitamin D influences the musculoskeletal system via the calcium-phosphorus metabolism and the receptors found in skeletal muscle cells (8). Vitamin D deficiency has been shown to decrease muscle strength, the this decrease in proximal muscles affect postural stability and can increase falls. Vitamin D deficiency also causes problems in bone mineralization, causing isolated or widespread pain in muscles, bones and joints. These patients end up getting wrong diagnoses such as fibromyalgia, osteoarthritis, inflammatory arthritis, and chronic fatigue syndrome (1,7). Vitamin D deficiency causes hyperinnervation and hypersensitivity on nerves and cause pain to be felt more intensely (5).
In a normal skeletal muscle, during an isometric contraction, a number of motor unit will be activated. These motor units produce a stable electromyography pattern and keep their own frequencies during contraction. If the nerve, tendon or a cutaneous nerve nearby is stimulated, electromyographic activity is disrupted and a bioelectric silence occurs. This is called cutaneous silent period (CSP). It is an inhibitory spinal reflex and its afferents consist of A-delta nerve fibers.
In various studies, CSP has been shown to be clinically beneficial in conditions like peripheral neuropathy, syringomyelia, Parkinson's disease, restless leg syndrome and fibromyalgia.
von Känel R et al. has investigated the effect of vitamin D deficiency on widespread pain index (WPI) and symptom severity score (SSS) and found out that it increases central sensitivity (8). In thei study, thy did not utilize any electrophysiologic objective measurements. Akyüz et al. have investigated the effect of vitamin D deficiency on chronic pain and nerve conduction studies; they have shown that vitamin D is correlated with various nerve conduction parameters while these parameters do not change after replacement (9,10).
Patients with vitamin D deficiency and healthy controls with normal vitamin D levels will be compared in terms of cutaneous silent period parameters, pain severity and neuropathic sensitization and quality of life. Cutaneous silent period parameters (duration and latency ), The Leeds Assessment of Neuropathic Symptoms \& Signs and Nottingham Health Profile will be used for the assessments. Patients with vitamin D deficiency will receive vitamin D supplementation therapy. Before and after therapy, cutaneous silent period parameters, LANSS scores and Nottingham Health Profile will measured before and 8 weeks after starting vitamin D supplementation therapy.
Study design
- Primary purpose
- Screening
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Interventional Arm | Experimental | Dietary Supplement: vitamin DPatients with vitamin D deficiency will receive vitamin D replacement therapy. Before and after therapy, cutaneous silent period will be measured from each upper extremity and latencies will be recorded. Their LANSS scores and Notthingham Health Profile will be recorded before and after treatment. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Presence of widespread pain
- Presence of vitamin D deficit
Key exclusion criteria (6 listed)
- Any contraindication of performing silent cutaneous period
- Any contraindication for vitamin d use
- Presence of conditions that affect cutaneous silent period like the presence of carpal tunnel syndrome and polyneuropathies
- Defective peripheric autonomic nervous system findings
- Not being able to write and read
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 |
|---|---|---|
| vitamin DVitamin D replacement | Dietary supplement | Interventional Arm |
Primary outcome
cutaneous silent period latency (ms)
Time frame: 8 weeks
the brief interruption in voluntary contraction that follows strong electrical stimulation (painful) of a cutaneous nerve
cutaneous silent period duration (ms)
Time frame: 8 weeks
the brief interruption in voluntary contraction that follows strong electrical stimulation (painful) of a cutaneous nerve
3 secondary outcomes
Visual analog scale (VAS) of pain
Time frame: 8 weeks
Leeds assessment of neuropathic symptoms and signs (LANSS)
Time frame: 8 weeks
The Nottingham Health Profile (NHP)
Time frame: 8 weeks
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 20 Dec 2018.
- Background: PubMed 14985208Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004 Mar;79(3):362-71. doi: 10.1093/ajcn/79.3.362.
- Background: PubMed 19807897Hamilton B. Vitamin D and human skeletal muscle. Scand J Med Sci Sports. 2010 Apr;20(2):182-90. doi: 10.1111/j.1600-0838.2009.01016.x. Epub 2009 Oct 5.
- Background: PubMed 21646368Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM; Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Jul;96(7):1911-30. doi: 10.1210/jc.2011-0385. Epub 2011 Jun 6.
- Background: PubMed 18400738Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008 Apr;87(4):1080S-6S. doi: 10.1093/ajcn/87.4.1080S.
- Background: PubMed 16095934Breivik H, Collett B, Ventafridda V, Cohen R, Gallacher D. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain. 2006 May;10(4):287-333. doi: 10.1016/j.ejpain.2005.06.009. Epub 2005 Aug 10.
- Background: PubMed 17377737Lotfi A, Abdel-Nasser AM, Hamdy A, Omran AA, El-Rehany MA. Hypovitaminosis D in female patients with chronic low back pain. Clin Rheumatol. 2007 Nov;26(11):1895-901. doi: 10.1007/s10067-007-0603-4. Epub 2007 Mar 22.
- Background: PubMed 17341569Wicherts IS, van Schoor NM, Boeke AJ, Visser M, Deeg DJ, Smit J, Knol DL, Lips P. Vitamin D status predicts physical performance and its decline in older persons. J Clin Endocrinol Metab. 2007 Jun;92(6):2058-65. doi: 10.1210/jc.2006-1525. Epub 2007 Mar 6.
- Background: PubMed 15497769Mascarenhas R, Mobarhan S. Hypovitaminosis D-induced pain. Nutr Rev. 2004 Sep;62(9):354-9. doi: 10.1111/j.1753-4887.2004.tb00061.x.
- Background: PubMed 1872673Gloth FM 3rd, Lindsay JM, Zelesnick LB, Greenough WB 3rd. Can vitamin D deficiency produce an unusual pain syndrome? Arch Intern Med. 1991 Aug;151(8):1662-4.
- Background: PubMed 22328176Haroon M, FitzGerald O. Vitamin D deficiency: subclinical and clinical consequences on musculoskeletal health. Curr Rheumatol Rep. 2012 Jun;14(3):286-93. doi: 10.1007/s11926-012-0244-8.
- Background: PubMed 21957236Tague SE, Clarke GL, Winter MK, McCarson KE, Wright DE, Smith PG. Vitamin D deficiency promotes skeletal muscle hypersensitivity and sensory hyperinnervation. J Neurosci. 2011 Sep 28;31(39):13728-38. doi: 10.1523/JNEUROSCI.3637-11.2011.
- Background: PubMed 24730754von Kanel R, Muller-Hartmannsgruber V, Kokinogenis G, Egloff N. Vitamin D and central hypersensitivity in patients with chronic pain. Pain Med. 2014 Sep;15(9):1609-18. doi: 10.1111/pme.12454. Epub 2014 Apr 14.
- Individual participant dataSharing planned: No
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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.
Ozge Kenis Coskun, MD principal investigator
Marmara University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing vitamin D in people with Vitamin D Deficiency and Central Sensitisation, run by Marmara University at 1 site in Turkey (Türkiye).
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 2 inclusion and 6 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 20 Dec 2018. 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 Turkey (Türkiye). 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.
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?
cutaneous silent period latency (ms) (time frame: 8 weeks). The study lists 2 primary outcomes in all. 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 NCT03420378, which also lists 14 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 20 Dec 2018.