Vitamin D for Painful Nocturnal Leg Cramps

Study Overview
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Brief Summary
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Research question: Does vitamin D reduce the frequency and severity of nocturnal leg cramps in older persons who previously took quinine for leg cramps? Experimental Design: This is a randomized, double blind, placebo controlled study of 70 men and women veterans receiving care at the Madison VA Medical Center(VAMC) or at the University of Wisconsin Hospitals and Clinics (UWHC). Individuals age 50 or more who have previously taken quinine for nocturnal leg cramps and meeting baseline criteria are eligible to enroll. Enrollees meeting laboratory criteria, including low-normal vitamin D levels, will undergo a 2-week diary run-in period to confirm cramp frequency. Those who report two or more leg cramps in each week will continue in the study and will be randomized to vitamin D or placebo. After a two-week wash-in, subjects will take a vitamin D capsule (50,000 units) once daily for 10 days, followed by a once weekly vitamin D (50,000 units) maintenance dose for 7 weeks. Subjects will record by diary the number and severity of leg cramps from the start of the diary run-in until a week after the last dose of study drug. Study investigators will call subjects at scheduled intervals to assess compliance, tolerability, and diary use. Major risks to subjects: No major risks are anticipated. Excessive vitamin D can increase blood calcium levels (hypercalcemia), with symptoms such as thirst, nausea, and weakness. However, symptomatic hypercalcemia has not been reported except for those taking more than 40,000 units daily for several months. This is far above the cumulative dose in our study. Potential benefits: Subjects may not receive any benefit. Vitamin D may alleviate leg cramps for subjects who receive it. Consent Procedure: Flyers describing the study and telephone contact information will be mailed to patients who have received quinine during the period 2002-2007. The PI or Co-PI will return calls to describe the study and answer any questions. For persons meeting preliminary (pre-lab) study criteria, two copies of the consent form will be mailed, with the patient mailing back one signed consent to the PI.

Detailed Description
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This is a randomized, double-blind, placebo-controlled trial to determine if oral vitamin D administration reduces the number or severity of nocturnal leg cramps, compared to placebo. Symptom diaries will be used throughout the study to assess frequency and severity of cramps. We will enroll a total of 70 men and women at least 50 years of age who have nocturnal leg cramps at least twice weekly and have previously received quinine for this. Those meeting baseline laboratory criteria and who report at least two leg cramps per week in a two-week diary run-in period will be randomized to vitamin D or placebo. Baseline, mid-study, and final laboratory testing will assess any changes in 25-hydroxyvitamin D(OHD) and related variables (25-hydroxyvitamin D is the best measure of vitamin D status.) The time from the beginning of the diary run-in through the final dose of drug and last labs,will be about 14 weeks. Optimal vitamin D status for health is unknown, although many experts aim for serum 25-hydroxyvitamin D of 35-40 ng/ml. Subjects in this study randomized to vitamin D will take a vitamin D capsule (50,000 units) once daily for 10 days, followed by a once weekly vitamin D (50,000 units) maintenance dose for 7 weeks. Based on published literature on the ability of vitamin D to raise serum 25-OHD over time, we estimate that the loading doses will boost levels after 10 days by an increment of  40ng/ml (up to  65 ng/mL total, starting with a typical person's baseline of 25ng/ml). This achieved level of 65 is within the reference range of our VA's reference range of 20-100. (In the PI's experience, most veterans without special D supplementation have baseline levels between 15 and 40).

Official Title
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Nocturnal Leg Cramps in the Elderly: Randomized Controlled Trial of Ergocalciferol (Vitamin D2) for a Painful and Distressing Problem

Conditions
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Leg Cramps, Nocturnal

Intervention / Treatment
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* Drug: vitamin d
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: One or more prescription for quinine at the Madison VA in the last 5 years, or else be a UWHC (U Wisconsin Health Clinics) patient whose UWHC medication list had quinine listed in the last five years At least 50 years of age, with women being past menopause. This is defined as the woman reporting no periods in the last 12 consecutive months or longer. Leg cramps listed in medical record, Ability & willingness to give informed consent, Stable estimated Glomerular filtration rate (GFR)>35 ml/min for the prior 6 mos, No change in diuretic therapy in last 3 months, Stable pattern of two or more cramps per week for past three months, Ability to complete daily diary entry, Post-consent: serum 25-OH of 20-45 ng/mL, albumin- corrected calcium <10.3 mg/dL, and urine calcium/creatinine ratio <0.25. Exclusion Criteria: Not receiving primary care at Madison VAMC, or at UWHC Hyperparathyroidism (1°, 2°, or 3°), Osteomalacia , Paget's disease, Metastatic cancer, Taking vitamin D 50,000 units capsules, Serum Ca++ >10.3 mg/dL in subject chart, Sarcoidosis or tuberculosis, and Peripheral vascular disease or other condition confounding assessment of cramps.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: vitamin D 50,000 U/d x 10d, + vitamin D 50,000 U weekly 7 wks<br>Vitamin D arm | Drug: vitamin d<br>* After a two-week wash-in, subjects will take a vitamin D capsule (50,000 units) once daily for 10 days, followed by a once weekly vitamin D (50,000 units) maintenance dose for 7 weeks.<br>* Other names: ergocalciferol;|
| Placebo Comparator: placebo x 10d, + placebo weekly 7 wks<br>placebo | Drug: placebo<br>* After a two-week wash-in, subjects will take a placebo capsule once daily for 10 days, followed by a once weekly maintenance dose for 7 weeks.<br>* Other names: lactose;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Nocturnal Leg Cramp Rate | Difference in number of leg cramps per day during treatment period compared to baseline period. Participants will undergo a 2-week diary run-in period to confirm cramp frequency. After a 2 week wash-in, subjects will take a vitamin D capsule (50,000 units) once daily for 10 days, followed by a once weekly vitamin D (50,000 units) maintenance dose for 7 weeks. Subjects will record by diary the number and severity of leg cramps from the start of the diary run-in until 1 week after the last dose of study drug/placebo. | baseline and 77 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Calcium Level | Serum calcium was measured to detect any possible correlation between high dose of Vitamin D and hypercalcemia. Hypercalcemia is defined as a serum calcium level greater than 10.5 mg/dL. | Day 77 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Leg cramps, vitamin D deficiency