Vitamin D for Painful Nocturnal Leg Cramps

• ClinicalTrials.gov Identifier: NCT00715429
• Recruitment Status: Terminated
• First Posted: July 15, 2008
• Results First Posted: September 17, 2019
• Last Update Posted: September 17, 2019
• Sponsor: University of Wisconsin, Madison
• Collaborator: Mayday Fund
• Information provided by (Responsible Party): University of Wisconsin, Madison

Tracking Information

• First Submitted Date: July 10, 2008
• First Posted Date: July 15, 2008
• Results First Submitted Date: December 11, 2013
• Results First Posted Date: September 17, 2019
• Last Update Posted Date: September 17, 2019
• Study Start Date: August 2007
• Actual Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 26, 2019)

Change in the Nocturnal Leg Cramp Rate [ Time Frame: baseline and 77 day ]

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.

• Original Primary Outcome Measures (submitted: July 14, 2008): Frequency and severity of nocturnal leg cramps [ Time Frame: two years ]

Current Secondary Outcome Measures (submitted: August 26, 2019)

Serum Calcium Level [ Time Frame: Day 77 ]

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.

• Original Secondary Outcome Measures (submitted: July 14, 2008): Hypercalcemia [ Time Frame: two years ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

Brief Summary

1. Research question: Does vitamin D reduce the frequency and severity of nocturnal leg cramps in older persons who previously took quinine for leg cramps?
2. 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.
3. 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.
4. Potential benefits: Subjects may not receive any benefit. Vitamin D may alleviate leg cramps for subjects who receive it.
5. 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

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).

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Leg Cramps, Nocturnal

Intervention

• Drug: vitamin d
  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.
  Other Name: ergocalciferol
• Drug: placebo
  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.
  Other Name: lactose

Study Arms

• Experimental: vitamin D 50,000 U/d x 10d, + vitamin D 50,000 U weekly 7 wks
  Vitamin D arm
  Intervention: Drug: vitamin d
• Placebo Comparator: placebo x 10d, + placebo weekly 7 wks
  placebo
  Intervention: Drug: placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: June 12, 2012): 29
• Original Estimated Enrollment (submitted: July 14, 2008): 70
• Actual Study Completion Date: August 2011
• Actual Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00715429
• Other Study ID Numbers: H-2007-0255
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: University of Wisconsin, Madison
• Original Responsible Party: Mary E. Elliott PharmD PhD, Associate Professor, School of Pharmacy, University of Wisconsin-Madison
• Current Study Sponsor: University of Wisconsin, Madison
• Original Study Sponsor: Same as current
• Collaborators: Mayday Fund

Investigators

• Principal Investigator: Mary E Elliott, PhD; University of Wisconsin, Madison

• PRS Account: University of Wisconsin, Madison
• Verification Date: August 2019