Calcium and Calcitriol Protocols for Hypoparathyroidism

Overseen By Jean-Philippe Vezina, MD, FRCSC

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: CHU de Quebec-Universite Laval

Disqualifiers: Neck dissection, Intellectual deficit, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

Duration: 4 weeks

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two methods to manage low calcium levels after thyroid surgery, a condition known as hypoparathyroidism. One group will receive standard treatment with calcium and calcitriol (a form of Vitamin D) immediately after surgery. The other group's treatment will be adjusted based on their PTH levels, a hormone that helps control calcium. The trial aims to determine which method better improves quality of life. Individuals who have had their thyroid fully or partially removed may qualify for this study. As an unphased trial, it offers participants the chance to contribute to valuable research that could enhance post-surgery care for future patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that calcium carbonate and calcitriol are generally safe for managing hypoparathyroidism. These treatments help stabilize calcium levels after thyroid surgery. Following dosing instructions carefully is crucial, as excessive intake can lead to milk-alkali syndrome, a condition that may cause serious health issues.

Long-term studies support the safety and effectiveness of parathyroid hormone (PTH) as a replacement therapy. Most patients in these studies reported positive results.

Both treatments are usually well-tolerated, but anyone considering them should consult their doctor to ensure suitability. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatment for hypoparathyroidism, which typically involves fixed doses of calcium carbonate and calcitriol, the new protocol being studied allows for personalized dosing. Researchers are excited because this approach could optimize calcium and calcitriol levels based on individual patient needs, particularly using post-operative PTH levels to guide treatment decisions. This personalized strategy might improve patient outcomes by reducing the risk of complications associated with over- or under-treatment.

What evidence suggests that this trial's treatments could be effective for hypoparathyroidism?

Past studies have commonly used calcium carbonate and calcitriol to manage hypoparathyroidism, especially after thyroid surgery. Calcium carbonate stabilizes blood calcium levels, while calcitriol, a form of vitamin D, aids calcium absorption. Research has shown that this combination can reduce symptoms like fatigue and cognitive issues. In this trial, one group of participants will receive empiric calcium and calcitriol repletion.

Another group will receive PTH-based calcium carbonate and calcitriol repletion. Treatments based on PTH (parathyroid hormone) have shown promising results in previous studies. Specifically, PTH has been found to maintain normal calcium levels more effectively and reduce the need for additional vitamin D. It has also been linked to improved quality of life by alleviating physical symptoms and reducing hospital visits. Both methods effectively manage the condition, but they operate in slightly different ways. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals who have undergone a total thyroidectomy or completion hemithyroidectomy and are dealing with hypoparathyroidism. Participants must be able to complete questionnaires in English or French, without severe psychiatric disorders, intellectual deficits, illiteracy, or the need for neck dissection.

Inclusion Criteria

I have had my entire thyroid or half of it surgically removed.

Exclusion Criteria

Unable to fill in questionnaires (intellectual deficit, severe psychiatric disorder, illiterate, does not speak French or English)

I need surgery to remove lymph nodes in my neck.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive calcium carbonate and calcitriol post-operatively, with monitoring of PTH levels to determine treatment protocol

4 weeks

2 visits (in-person) at 1 week and 4 weeks post-op

Follow-up

Participants are monitored for quality of life, symptoms of hypocalcemia, and adverse effects of treatment

4 weeks

2 visits (in-person) at 1 week and 4 weeks post-op

What Are the Treatments Tested in This Trial?

Interventions

• Empiric use of Calcium Carbonate and Calcitriol
• PTH based Calcium Carbonate and Calcitriol repletion

Trial Overview The study compares two treatment protocols for managing low parathyroid hormone levels after thyroid surgery: one uses PTH levels to determine calcium and vitamin D dosing (Calcitriol), while the other uses a fixed dose regardless of PTH levels.

How Is the Trial Designed?

Group I: PTH based repletion group Experimental Treatment 1 Intervention

Patients in this group will be prescribed calcium carbonate and calcitriol based on their post-operative PTH.

Group II: Empiric calcium and calcitriol repletion group Experimental Treatment 1 Intervention

All patients in this group will receive post-operative calcium carbonate and calcitriol.

Empiric use of Calcium Carbonate and Calcitriol is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Calcium carbonate for:

• Symptomatic relief of heartburn, acid indigestion, and sour stomach
• Calcium supplementation
• Post-thyroidectomy hypocalcemia management

Approved in European Union as Calcium carbonate for:

• Symptomatic relief of heartburn, acid indigestion, and sour stomach
• Calcium supplementation
• Post-thyroidectomy hypocalcemia management

Approved in Canada as Calcium carbonate for:

• Symptomatic relief of heartburn, acid indigestion, and sour stomach
• Calcium supplementation
• Post-thyroidectomy hypocalcemia management

Who Is Running the Clinical Trial?

CHU de Quebec-Universite Laval

Lead Sponsor

Trials

177

Recruited

110,000+

Published Research Related to This Trial

A 17-year-old girl with surgically induced hypoparathyroidism showed severe hypocalcemia that did not respond to high doses of vitamin D and oral calcium, requiring intravenous calcium gluconate for tetany correction.

Oral administration of a 10% calcium chloride solution effectively normalized serum calcium levels within hours, suggesting that achlorhydria may hinder the absorption of oral calcium supplements, and highlighting the need for careful monitoring to prevent hyperchloremic acidosis during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral calcium chloride in hypoparathyroidism refractory to massive doses of calcium carbonate and vitamin D. Komindr, S., Schmidt, LW., Palmieri, GM.[2019]

In a study involving 25 postmenopausal women, calcium citrate was found to be 46% more effective than calcium carbonate in raising serum calcium levels after a meal, indicating higher bioavailability.

Calcium citrate also led to a greater reduction in parathyroid hormone levels compared to calcium carbonate, suggesting it may be more effective in supporting bone health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and pharmacodynamic comparison of two calcium supplements in postmenopausal women. Heller, HJ., Greer, LG., Haynes, SD., et al.[2013]

In a study involving seven patients, two alternative calcium carbonate preparations (Calcium-500 and Calcichew) were found to be effective phosphate binders at a significantly lower dosage compared to the commonly prescribed Titralac, which requires up to 12 tablets daily.

Both alternative preparations did not cause significant changes in serum calcium and phosphate levels, suggesting they are safe options that can improve patient compliance and reduce treatment costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calcium carbonate 1250 mg/1260 mg: an effective phosphate binder. Taylor, JE., Henderson, IS., Stewart, WK., et al.[2017]

In a study involving 12 healthy male volunteers, both calcium carbonate plus magnesium carbonate and hydrotalcite were found to have similar antacid efficacy, effectively neutralizing stomach acid for about one hour after administration.

Neither treatment caused acid 'rebound' effects, meaning that there was no increase in stomach acidity after the antacids wore off, indicating a safe profile for both medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absence of rebound effect with calcium carbonate. Simoneau, G.[2018]

Milk-Alkali syndrome, characterized by hypercalcemia, metabolic alkalosis, and renal impairment, can occur due to excessive use of over-the-counter calcium antacids like Tums®, highlighting the need for awareness of this condition.

The management of Milk-Alkali syndrome involves early diagnosis, discontinuation of calcium supplements, and intravenous hydration, which are crucial for effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No more milk in milk-alkali syndrome: a case report. Almusawi, A., Alhawaj, S., Al-Mousawi, M., et al.[2021]

In a review of 297 heart and heart-lung transplant recipients, 65 patients developed significant hypercalcemia, likely due to the long-term use of calcium carbonate antacid therapy prescribed to prevent peptic ulcer disease and osteoporosis.

Most patients with hypercalcemia returned to normal calcium levels after stopping calcium carbonate, but severe cases required intravenous hydration and diuretics, highlighting the need for careful monitoring of calcium levels in patients on this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Milk-alkali syndrome in patients treated with calcium carbonate after cardiac transplantation. Kapsner, P., Langsdorf, L., Marcus, R., et al.[2023]

Conventional treatment for hypoparathyroidism involves oral calcium and vitamin D supplements, with calcium carbonate being the most common choice due to its higher elemental calcium content.

Calcium citrate is recommended for patients with low stomach acid, and clinicians often increase the dose of activated vitamin D to minimize the need for calcium supplements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conventional Treatment of Hypoparathyroidism. Babey, M., Brandi, ML., Shoback, D.[2019]

Calcium supplementation is important for preventing and treating conditions like osteoporosis and hypertension, especially in North America where dietary intake is often low.

Chelated calcium and refined calcium carbonate supplements are generally safe and effective for most people, but it's crucial not to exceed 2,000 mg of calcium without medical advice due to potential risks like mineral deficiencies and milk-alkali syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calcium supplementation. Whiting, SJ., Wood, R., Kim, K.[2023]

In a study involving 83 subjects, the aluminum/magnesium hydroxide antacid (Mylanta Double-Strength) was found to be more effective than calcium carbonate (Tums E-X) in increasing esophageal pH, with a faster onset and longer duration of action (82 minutes vs. 60 minutes).

Only the aluminum/magnesium hydroxide formulation significantly increased gastric pH compared to placebo, while calcium carbonate often resulted in an 'acid rebound' effect, indicating that the primary action of both antacids is in the lower esophagus for heartburn relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Aluminum/Magnesium Hydroxide and Calcium Carbonate on Esophageal and Gastric pH in Subjects with Heartburn. Decktor, DL., Robinson, M., Maton, PN., et al.[2019]

Current American guidelines recommend calcium citrate for patients using antacids, but there is no strong scientific evidence to support this preference over calcium carbonate.

Calcium absorption may be improved when taken with meals, regardless of whether calcium citrate or calcium carbonate is used, indicating that meal timing could be an important factor in calcium supplementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Calcium suppletion for patients who use gastric acid inhibitors: calcium citrate or calcium carbonate?]. de Jonge, HJ., Gans, RO., Huls, G.[2013]

In a study involving 12 women with hypoparathyroidism after total thyroidectomy, calcium carbonate intake in different forms (fasting, with water, orange juice, and breakfast) resulted in similar serum levels of calcium and phosphorus, indicating that the form of intake may not significantly affect absorption.

The maximum serum levels of calcium and phosphorus were comparable across all intake methods, suggesting that patients can take calcium carbonate with or without food or juice without impacting its effectiveness in managing hypocalcemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypoparathyroidism: what is the best calcium carbonate supplementation intake form? Gollino, L., Biagioni, MFG., Sabatini, NR., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5393596/

Management of Hypoparathyroidism: Present and Future - PMC The normal daily production rate of calcitriol is 0.5–1 μg/d (10). In hypoparathyroidism, the lack of PTH is associated with lower calcitriol levels, hence ...

2. chi.gov.sa chi.gov.sa/Style%20Library/IDF_Branding/Indication/106%20-%20Hypoparathyroidism-New%20Indication.pdf

HYPOPARATHYROIDISM • Calcium carbonate, which contains 40% elemental calcium, and calcium citrate, with 21% elemental calcium, are the most used forms of calcium supplements ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/12970289/

Long-term treatment of hypoparathyroidism - PubMed - NIH We conclude that treatment with twice daily sc PTH provides a safe and effective alternative to calcitriol therapy and is able to maintain normal serum calcium ...

4. aot.amegroups.org aot.amegroups.org/article/view/7135/html

the impact of permanent post-operative hypoparathyroidism ... Permanent post-operative hypoparathyroidism reduces quality of life, causing symptoms like fatigue, cognitive deficits, and neuropsychiatric issues, and ...

5. endocrinepractice.org endocrinepractice.org/article/S1530-891X(23)00022-8/fulltext

A Parathyroid Hormone–Guided Calcium and Calcitriol ... A PTH-guided protocol for Ca and calcitriol supplementation significantly reduces the postoperative hypocalcemia and hospital readmission rates in patients ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10118816/

Treatment options in hypoparathyroidism - PMC Calcium carbonate is the most available form and needs to be administered with meals to increase its absorption whereas calcium citrate does not have the same ...

7. withpower.com withpower.com/trial/phase-hypoparathyroidism-8-2017-70567

Calcium and Calcitriol Protocols for Hypoparathyroidism Calcium carbonate and calcitriol are generally safe for most people when used as directed, but excessive intake can lead to milk-alkali syndrome, which causes ...

8. liebertpub.com liebertpub.com/doi/10.1089/thy.2017.0309

American Thyroid Association Statement on Postoperative ... Oral calcium carbonate is the most widely available and inexpensive preparation, and is given as 500–625 mg to 1000–1250 mg two to three times a day. Routine ...