Theophylline for Pseudohypoparathyroidism

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Ashley Shoemaker

Must not be taking: Theophylline

Disqualifiers: Seizure disorder, Cardiac arrhythmia, Hepatic insufficiency, Congestive heart failure, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

34 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial will test theophylline, a medication that helps relax muscles, in children and young adults with a genetic disorder called pseudohypoparathyroidism. The goal is to see if it can help them lose weight, handle sugar better, and respond better to hormones.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using medications that affect theophylline levels.

What evidence supports the effectiveness of the drug Theophylline ER for treating pseudohypoparathyroidism?

Research shows that Theophylline, a phosphodiesterase inhibitor, can increase urinary phosphate and cAMP excretion in patients with pseudohypoparathyroidism type II, suggesting it may help improve the body's response to parathyroid hormone. ^{1 2 3 4 5}

How does the drug Theophylline ER differ from other treatments for pseudohypoparathyroidism?

Theophylline ER is unique because it acts as a phosphodiesterase inhibitor, which can increase urinary phosphate and cAMP excretion, potentially addressing the underlying issue of cAMP unresponsiveness in pseudohypoparathyroidism. This mechanism is different from other treatments like vitamin D, which primarily focus on correcting calcium and phosphate levels. ^{1 3 4 6 7}

Research Team

Ashley Shoemaker, MD, MSCI

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

This trial is for children and young adults who have completed a previous theophylline study for pseudohypoparathyroidism. It's not open to those with seizure disorders, liver issues, active ulcers, heart failure, arrhythmias (except bradycardia), or those on certain meds. Pregnant individuals, smokers and heavy drinkers are also excluded.

Inclusion Criteria

Successful completion of the randomized clinical trial "Phase 2 Study of Theophylline Treatment of Pseudohypoparathyroidism IND 133103 (11/1/2016)"

Exclusion Criteria

You are currently smoking cigarettes or abusing alcohol.

Unable to comply with study procedures in the opinion of the investigator

I have been diagnosed with congestive heart failure.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral theophylline, either as a once daily capsule or q6h elixir, to evaluate its efficacy in treating pseudohypoparathyroidism

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue receiving theophylline to evaluate long-term safety and changes in BMI, hormone resistance, and epiphyseal closure

24 months

Treatment Details

Interventions

• Theophylline ER

Trial Overview The trial is testing if Theophylline ER can help with weight loss, glucose tolerance and hormone resistance in patients with pseudohypoparathyroidism. This phase 2 trial follows up from an earlier study to further evaluate the drug's effectiveness.

Participant Groups

Group I: Open-label theophylline Experimental Treatment 1 Intervention

Oral theophylline - either once daily capsule or q6h elixir.

Who Is Running the Clinical Trial?

Ashley Shoemaker

Lead Sponsor

Trials

1

Recruited

30+

Findings from Research

In children with pseudohypoparathyroidism (PHP), resistance to parathyroid hormone can be overcome with vitamin D treatment, suggesting a potential therapeutic approach for managing the disorder.

The study identified low levels of urinary cAMP, which is crucial for parathyroid hormone signaling, as a key diagnostic marker for PHP, indicating that the disorder is linked to a failure in the second messenger system rather than a lack of hormone production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Investigations of the urinary cAMP-excretion in pseudohypoparathyroidism (author's transl)]. Stögmann, W.[2013]

The 58-year-old woman diagnosed with pseudohypoparathyroidism type II showed increased urinary phosphate and cAMP excretion after treatment with the phosphodiesterase inhibitor theophylline, indicating a potential therapeutic approach for this condition.

High doses of cAMP or long-term use of phosphodiesterase inhibitors can restore the responsiveness of urinary phosphate secretion, suggesting that cAMP signaling in the kidneys may be a key factor in managing PHP type II.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased urinary phosphate excretion in pseudohypoparathyroidism type II with long-term treatment with phosphodiesterase inhibitor. Mano, T., Uchimura, K., Hayashi, R., et al.[2015]

In two young infants with transitory pseudohypoparathyroidism, high doses of vitamin D were ineffective, but treatment with 1.25-(OH)2-D3 (Rocaltrol) quickly corrected metabolic abnormalities like hypocalcemia and hyperphosphatemia.

Monitoring urinary cAMP excretion levels helped differentiate between transient and permanent forms of the disease, with specific values indicating when treatment could be safely stopped.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Transitory pseudohypoparathyroidism in the newborn infant]. Schaumberger, E., Hohenauer, L., Sommer, R.[2013]

References

1. Austria pubmed.ncbi.nlm.nih.gov

[Investigations of the urinary cAMP-excretion in pseudohypoparathyroidism (author's transl)]. [2013]

2. United States pubmed.ncbi.nlm.nih.gov

Studies on the attainment of normocalcemia in patients with pseudohypoparathyroidism. [2019]

3. Germany pubmed.ncbi.nlm.nih.gov

Increased urinary phosphate excretion in pseudohypoparathyroidism type II with long-term treatment with phosphodiesterase inhibitor. [2015]

4. United States pubmed.ncbi.nlm.nih.gov

Pseudohypoparathyroidism: defective excretion of 3',5'-AMP in response to parathyroid hormone. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

[Pseudohypoparathyroidism and adrenal cortex insufficiency. A case of multiple endocrinopathy due to peripheral hormone resistance]. [2019]

6. Germany pubmed.ncbi.nlm.nih.gov

[Transitory pseudohypoparathyroidism in the newborn infant]. [2013]

7. Japan pubmed.ncbi.nlm.nih.gov

Effect of 1alphaOH-vitamin D3 in a case of pseudohypoparathyroidism. [2019]