Is Treatment of Vitamin D Deficiency Associated With Resolution of Statin-Induced Muscular Symptoms
| Status: | Recruiting |
|---|---|
| Conditions: | Gastrointestinal |
| Therapuetic Areas: | Gastroenterology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 12/16/2018 |
| Start Date: | March 2012 |
| End Date: | March 2019 |
| Contact: | Ying Mou, PhD |
| Email: | ying.mou@cshs.org |
| Phone: | 310-248-7669 |
Statins are a class of drugs that are highly effective at lowering cholesterol levels.
However, compliance is often limited by symptoms of muscle pain. The investigators would like
to study Vitamin-D deficient individuals who also have muscle pain due to statin use. About 1
billion people are estimated to have low or insufficient levels of vitamin D worldwide.
Patients with low or insufficient levels of vitamin D may develop muscle disease. The purpose
of this study is to identify if these symptoms are associated with vitamin D deficiency, and
most importantly, if treatment of vitamin D deficiency can reduce muscle pain that is caused
by statin treatment.
However, compliance is often limited by symptoms of muscle pain. The investigators would like
to study Vitamin-D deficient individuals who also have muscle pain due to statin use. About 1
billion people are estimated to have low or insufficient levels of vitamin D worldwide.
Patients with low or insufficient levels of vitamin D may develop muscle disease. The purpose
of this study is to identify if these symptoms are associated with vitamin D deficiency, and
most importantly, if treatment of vitamin D deficiency can reduce muscle pain that is caused
by statin treatment.
Vitamin D2 (Ergocalciferol) is approved by the FDA to treat Vitamin D deficiency and will be
given according to approved labeling. This drug has not been systematically studied to test
the potential benefits of Vitamin D in patients who suffer from statin-induced muscle pain.
Vitamin D2 is the current standard of care for treating vitamin D deficiency. Since the
investigators are using Vitamin D2 therapy to treat vitamin D deficiency, and because our
trial is a pilot study, the data will not be submitted to the FDA for consideration of
changing the labeled indications for Vitamin D2 therapy.
This is a randomized, double-blinded, and placebo-controlled pilot study that will only be
performed at CSMC. 40 females with moderate to severe myopathic pain while on Simvastatin
will be enrolled in this study and will be randomized at a 1:1 ratio. Patients who will be
approached are considering an alternative statin medication as part of their clinical care to
address their muscle pain.
Participants will be recruited from the investigators' clinic patients. The study will be
discussed with a patient during clinical visit by the treating doctor. Interested individuals
will be provided with a copy of the consent form to take home for review with friends,
family, and other physicians. The patient may then call the study staff to set a study
appointment or enroll in the study during the clinical visit. A study investigator will
discuss the study with the patient and ask the patient to read through the consent. The
investigator will encourage the patient to ask any questions or discuss any concerns she
might have.
If the consenting investigator is also the patient's treating doctor, the consenting
investigator will request that the study coordinator approach the patient to determine the
patient's interest in the study in order to avoid a conflict of interest. The coordinator
will explicitly tell the patient that the patient's participation in the study is completely
voluntary and that the patient's medical care will not be affected should she choose not to
participate.
Participation in this study will be approximately 8 weeks. 20 participants will be randomized
to the treatment group and 20 to the placebo group. The treatment group will receive Vitamin
D2 therapy at 50,000 IU for 8 weeks (once per week) while the placebo group will receive a
placebo pill (once per week) that is identical in nature. Participants have 2 study visits
respectively at Week 0 and Week 8, and 1 phone follow-up visit at Week 1. In addition to the
administration of Vitamin D2 or placebo mentioned above, other study procedures include
informed consent, physical exam, questionnaires (brief pain assessment, and SF-12 to assess
limitations on physical activity), review of medical records, medication and supplement
review, blood draw, and phone followup. Subjects will be asked to stop any supplemental
Vitamin D therapy to maintain an equal dose within patients in the Vitamin D2 and placebo
group.
Prior to randomization, statin medication will be changed from Simvastatin to Atorvastatin
and patients will be followed up by telephone at Week 1 for tolerability of the new statin
medication. When a patient is intolerant to a particular statin, it is the standard of care
to attempt another statin medication. Typically, many choose atorvastatin since a lower dose
of the drug can be used to obtain the same target LDL/HDL, and lower doses reduce the risk of
toxicity. This change in medication would be preformed regardless of the research protocol.
Since the statin will be switched to a lower dose, it is possible that it will be a
confounding factor, however, even the placebo group will be switched to the same alternate
statin, reducing the differences between the two groups. In addition, Atorvastatin is also
metabolized by the CYP3A4 enzyme, and because the presumed mechanism of association between
vitamin D deficiency and statin-induced myopathic pain pivots on this enzyme, the
investigators wanted to choose a statin that continues to utilize this enzyme. But, for
reasons stated above, Atorvastatin has less myopathic symptoms due to lower doses used.
At the conclusion of the study, those in the treatment group whose serum 25 OH D levels have
reached > 30ng/mL (therapeutic) may continue on maintenance doses on ergocalciferol (1,000
Units/day) if they are receiving clinical benefit. For those whose 25 OH D levels are <
30ng/mL, regardless of whether they received clinical benefit or not from the treatment arm,
they will be offered a repeated 8 week course of Ergocalciferol therapy at 50,000 Units/week
under standard of care. It will be up to the patient to accept or decline the therapy.
given according to approved labeling. This drug has not been systematically studied to test
the potential benefits of Vitamin D in patients who suffer from statin-induced muscle pain.
Vitamin D2 is the current standard of care for treating vitamin D deficiency. Since the
investigators are using Vitamin D2 therapy to treat vitamin D deficiency, and because our
trial is a pilot study, the data will not be submitted to the FDA for consideration of
changing the labeled indications for Vitamin D2 therapy.
This is a randomized, double-blinded, and placebo-controlled pilot study that will only be
performed at CSMC. 40 females with moderate to severe myopathic pain while on Simvastatin
will be enrolled in this study and will be randomized at a 1:1 ratio. Patients who will be
approached are considering an alternative statin medication as part of their clinical care to
address their muscle pain.
Participants will be recruited from the investigators' clinic patients. The study will be
discussed with a patient during clinical visit by the treating doctor. Interested individuals
will be provided with a copy of the consent form to take home for review with friends,
family, and other physicians. The patient may then call the study staff to set a study
appointment or enroll in the study during the clinical visit. A study investigator will
discuss the study with the patient and ask the patient to read through the consent. The
investigator will encourage the patient to ask any questions or discuss any concerns she
might have.
If the consenting investigator is also the patient's treating doctor, the consenting
investigator will request that the study coordinator approach the patient to determine the
patient's interest in the study in order to avoid a conflict of interest. The coordinator
will explicitly tell the patient that the patient's participation in the study is completely
voluntary and that the patient's medical care will not be affected should she choose not to
participate.
Participation in this study will be approximately 8 weeks. 20 participants will be randomized
to the treatment group and 20 to the placebo group. The treatment group will receive Vitamin
D2 therapy at 50,000 IU for 8 weeks (once per week) while the placebo group will receive a
placebo pill (once per week) that is identical in nature. Participants have 2 study visits
respectively at Week 0 and Week 8, and 1 phone follow-up visit at Week 1. In addition to the
administration of Vitamin D2 or placebo mentioned above, other study procedures include
informed consent, physical exam, questionnaires (brief pain assessment, and SF-12 to assess
limitations on physical activity), review of medical records, medication and supplement
review, blood draw, and phone followup. Subjects will be asked to stop any supplemental
Vitamin D therapy to maintain an equal dose within patients in the Vitamin D2 and placebo
group.
Prior to randomization, statin medication will be changed from Simvastatin to Atorvastatin
and patients will be followed up by telephone at Week 1 for tolerability of the new statin
medication. When a patient is intolerant to a particular statin, it is the standard of care
to attempt another statin medication. Typically, many choose atorvastatin since a lower dose
of the drug can be used to obtain the same target LDL/HDL, and lower doses reduce the risk of
toxicity. This change in medication would be preformed regardless of the research protocol.
Since the statin will be switched to a lower dose, it is possible that it will be a
confounding factor, however, even the placebo group will be switched to the same alternate
statin, reducing the differences between the two groups. In addition, Atorvastatin is also
metabolized by the CYP3A4 enzyme, and because the presumed mechanism of association between
vitamin D deficiency and statin-induced myopathic pain pivots on this enzyme, the
investigators wanted to choose a statin that continues to utilize this enzyme. But, for
reasons stated above, Atorvastatin has less myopathic symptoms due to lower doses used.
At the conclusion of the study, those in the treatment group whose serum 25 OH D levels have
reached > 30ng/mL (therapeutic) may continue on maintenance doses on ergocalciferol (1,000
Units/day) if they are receiving clinical benefit. For those whose 25 OH D levels are <
30ng/mL, regardless of whether they received clinical benefit or not from the treatment arm,
they will be offered a repeated 8 week course of Ergocalciferol therapy at 50,000 Units/week
under standard of care. It will be up to the patient to accept or decline the therapy.
Inclusion Criteria:
1. Female gender (refer to section 4)
2. Age > 18, using an effective form of contraception (refer to section 4)
3. An indication to be on statin therapy
4. Moderate to severe myopathic pain while on Simvastatin
5. Serum CK level < 10 x ULN
6. Vitamin 25 OH D level < 30 ng/mL (as secondary hyperparathyroidism is triggered below
this level)1
7. English speaking patients only
8. Myopathic pain that cannot be attributed to other medical conditions
9. Continue a statin within the CYP3A4 family
10. Competent to give informed consent
Exclusion Criteria:
1. Clinical diagnosis of overt vitamin D deficiency: osteomalacia, rickets, hypocalcemia,
hypophosphatemia
2. Already taking Vitamin D supplements > 1000 IU/day
3. Serum creatinine > 2.2 mg/dL within last 6 months
4. AST/ALT > 3 x ULN of the local reference range
5. Serum CK level > 10 x ULN
6. Systolic blood pressure < 100 mmHg
7. Albumin adjusted calcium > 2.55 mmol/L or < 2.20 mmol/L
8. Renal osteodystrophy
9. Malabsorption syndrome
10. Metastatic malignancy
11. Transplant recipients
12. A co-existent diagnosis of renal calculi within the previous 6 months
13. A co-existent diagnosis of primary hyperparathyroidism within the previous 6 months
14. Recent therapy with corticosteroids within the previous 6 months
15. Currently consuming Digoxin, as usage increases risk of hypercalcemia
16. Lactating women
We found this trial at
1
site
8700 Beverly Blvd # 8211
Los Angeles, California 90048
Los Angeles, California 90048
(1-800-233-2771)
Phone: 310-248-7669
Cedars Sinai Med Ctr Cedars-Sinai is known for providing the highest quality patient care. Our...
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