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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of theophylline, a medication, for treating pseudohypoparathyroidism, a rare genetic disorder. People with this condition often experience weight gain, short stature, hormone resistance, and cognitive challenges. The trial aims to determine if theophylline can aid in weight loss, improve blood sugar levels, and reduce hormone resistance in children and young adults. Ideal participants have previously completed a related theophylline trial for pseudohypoparathyroidism. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants the chance to contribute to important findings.

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.

Is there any evidence suggesting that theophylline ER is likely to be safe for humans?

Research has shown that theophylline, a drug tested for pseudohypoparathyroidism, has been well-tolerated in clinical trials. Ongoing studies indicate that the drug and procedures have generally been safe for participants, with no major safety issues reported so far. This suggests that theophylline is likely safe, although individual experiences may differ. It is always important to discuss any concerns with a doctor before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pseudohypoparathyroidism?

Unlike the standard treatments for pseudohypoparathyroidism, which typically include calcium and active vitamin D supplements to manage symptoms, theophylline offers a unique approach. Theophylline is an experimental treatment that acts by potentially enhancing the body's response to parathyroid hormone, which might directly address the underlying hormonal resistance seen in this condition. Researchers are excited because this approach could improve the effectiveness of treatment and reduce the reliance on traditional supplements, offering a more targeted way to manage pseudohypoparathyroidism.

What evidence suggests that theophylline might be an effective treatment for pseudohypoparathyroidism?

Research has shown that theophylline, which participants in this trial will receive, might alleviate symptoms of pseudohypoparathyroidism, a genetic disorder. Studies have found that theophylline can lead to weight loss and better control of blood sugar levels. It may also reduce hormone resistance and support growth in children and young adults. One study discovered that theophylline boosts the effect of a hormone that helps the body use vitamin D, which is important for healthy bones. Overall, early evidence suggests theophylline could be a promising treatment for this condition. ^{2 3 5 6 7}

Who Is on the Research Team?

Ashley Shoemaker, MD, MSCI

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03029429?term=UNIPHYL&viewType=Table&rank=8

Theophylline Treatment for Pseudohypoparathyroidism The investigators hypothesize that theophylline will cause weight loss, improve glucose tolerance and slow growth plate closure in children and young adults.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10553654/

FRI596 Randomized Clinical Trial Of Theophylline For ... The primary outcome is change in BMI, expressed as % of the 95th %ile (BMI95), to account for age and gender. Secondary endpoints include ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03718403?term=UNIPHYL&viewType=Table&rank=4

Effect of Theophylline in Pseudohypoparathyroidism The study evaluates the effect of theophylline in 100 subjects with Pseudohypoparathyroidism. ... It is an open label intervention study for the off-label use of ...

4. withpower.com withpower.com/trial/phase-3-pseudopseudohypoparathyroidism-8-2018-c96fa

Theophylline for Pseudohypoparathyroidism The presence of theophylline enhances the effect of bPTH on 1,25-(OH)2D3 production, achieving a 170% increase at a lower bPTH concentration (2 ng/ml), ...

5. vanderbilt.trialstoday.org vanderbilt.trialstoday.org/trial/NCT03029429

Theophylline Treatment for Pseudohypoparathyroidism The investigators hypothesize that theophylline will cause weight loss, improve glucose tolerance and slow growth plate closure in children and ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04240821

Theophylline for Treatment of Pseudohypoparathyroidism The primary objective of this study is to evaluate the long-term safety of theophylline in patients with PHP. The secondary objectives of this study are to ...

7. withpower.com withpower.com/trial/phase-3-pseudohypoparathyroidism-4-2020-a4ad9

Theophylline for Pseudohypoparathyroidism Research shows that Theophylline, a phosphodiesterase inhibitor, can increase urinary phosphate and cAMP excretion in patients with pseudohypoparathyroidism ...