PB for Nephrogenic Diabetes Insipidus

(SerendipityPB1 Trial)

Recruiting at 1 trial location

Overseen By Taylor Cunningham

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must be taking: Tolvaptan

Disqualifiers: Gout, Hyperuricemia, Diabetes, 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: 15

Duration: 90 days

36 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you have high blood pressure, it must be controlled with medication for at least 30 days before starting the trial.

Is PB safe for use in humans?

The safety of parathyroid hormone (PTH) treatments, like teriparatide, has been studied for conditions like osteoporosis. It is generally considered safe, but there are concerns about potential side effects like high calcium levels in the blood and urine, and a warning about bone cancer risk in animal studies. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial is testing a drug called PB to see if it can help people who urinate frequently due to certain kidney conditions or treatments. It aims to help the kidneys manage water better, so patients don't have to go to the bathroom as often.

Research Team

Fouad Chebib, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for adults who can consent and have been diagnosed with nephrogenic diabetes insipidus (inherited or from lithium/tolvaptan use), ADPKD, or severe polyuria. They must have a GFR ≥ 30 ml/min, low morning urine concentration, and controlled blood pressure if hypertensive. Excluded are those with chronic diseases like heart failure or liver disease, urinary issues, recent gout attacks, uncontrolled gout/hyperuricemia, drug allergies to PB, or past hepatotoxicity from tolvaptan.

Inclusion Criteria

Only females are eligible for this study.

You have been diagnosed with nephrogenic diabetes insipidus (NDI), which can be either genetic or caused by certain medications.

You have kidney problems caused by taking lithium.

Exclusion Criteria

You have a history of low sodium levels in your blood that has lasted for a long time.

You have a significant long-term health condition like heart failure, diabetes, liver disease, or consistently high liver enzyme levels.

You have trouble controlling your bladder or have problems with urination.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PB to assess its efficacy in decreasing urine output and increasing urine osmolality

90 days

Visits at baseline, day 15, day 45, day 75

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• PB

Trial Overview The study tests the medication PB's effectiveness in reducing excessive urination in patients with inherited nephrogenic diabetes insipidus (NDI), NDI due to long-term treatment of ADPKD with tolvaptan, or NDI caused by previous lithium therapy.

Participant Groups

Group I: Polyuric subjects with Hereditary Nephrogenic Diabetes Insipidus Experimental Treatment 1 Intervention

Polyuric subjects with hereditary nephrogenic diabetes insipidus with loss of function of arginine vasopressin receptor 2 (AVPR2) or aquaporin 2 (AQP2) will be treated with PB

Group II: Polyuric subjects with Autosomal Dominant Polycystic Kidney Disease treated with Tolvaptan Experimental Treatment 1 Intervention

Polyuric subjects with autosomal dominant polycystic kidney disease on chronic tolvaptan treatment will be treated with PB

Group III: Polyuric subject secondary to lithium administration Experimental Treatment 1 Intervention

Polyuric subject post lithium administration will receive PB

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Otsuka America Pharmaceutical

Industry Sponsor

Trials

67

Recruited

28,400+

Tarek Rabah

Otsuka America Pharmaceutical

Chief Executive Officer since 2022

BS in Biology and BA in Business from the American University of Beirut, MBA from McGill University

John Kraus

Otsuka America Pharmaceutical

Chief Medical Officer since 2021

MD and PhD in Neurobiology from Duke University

Hopital du Sacre-Coeur de Montreal

Collaborator

Trials

52

Recruited

12,100+

Findings from Research

Parathyroidectomy (PTX) significantly reduced blood lead (Pb) levels in 30 patients with refractory secondary hyperparathyroidism (SHPT) undergoing long-term hemodialysis, indicating a beneficial effect on lead release from bone stores.

The study found that after PTX, there was a marked decrease in serum intact parathyroid hormone (iPTH) and a progressive increase in bone-specific alkaline phosphatase (BAP), suggesting that PTX effectively alters bone remodeling and may help mitigate lead exposure in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parathyroidectomy leads to decreased blood lead levels in patients with refractory secondary hyperparathyroidism. Chu, P., Wu, CC., Chen, CC., et al.[2016]

In a study of 28 patients with secondary hyperparathyroidism undergoing hemodialysis, intravenous calcitriol therapy for 16 weeks significantly reduced blood lead levels and markers of bone remodeling, indicating its efficacy in managing these conditions.

The therapy led to a notable decrease in serum intact parathyroid hormone (iPTH) levels and a positive correlation was found between blood lead levels and both serum iPTH and TRAP, suggesting that hyperparathyroidism may enhance lead mobilization from bones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decreased blood lead levels after calcitriol treatment in hemodialysis patients with secondary hyperparathyroidism. Lu, KC., Wu, CC., Ma, WY., et al.[2016]

PTH-1-37 is rapidly absorbed after subcutaneous injection, with a median time to peak concentration of 30 minutes, and has a short elimination half-life, indicating it acts quickly in the body.

The study demonstrated that PTH-1-37 effectively increases serum calcium levels in a dose-dependent manner and is well tolerated, with no serious adverse events reported, making it a promising candidate for treating calcium metabolism disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and Pharmacodynamic Characteristics of Subcutaneously Applied PTH-1-37. Forssmann, WG., Tillmann, HC., Hock, D., et al.[2022]

Teriparatide, a treatment for postmenopausal osteoporosis and osteoporosis in men, has been used for over 5 years, providing substantial data on its long-term safety, particularly regarding its registered dose of 20 microg/day.

While teriparatide is effective, there are important safety considerations, including the potential for hypercalcemia, hypercalciuria, and hyperuricemia, as well as a 'black-box' warning from the FDA about the risk of osteogenic sarcoma observed in rat studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of parathyroid hormone for the treatment of osteoporosis. Miller, PD.[2021]

Both parathyrin and calcitonin significantly reduce phosphate reabsorption in the kidneys, as demonstrated by microinfusion studies in anesthetized rats, indicating their direct renal effects.

The study found that the phosphaturic actions of parathyrin and calcitonin are additive, suggesting they operate through different mechanisms or nephron sites to influence phosphate metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Additive phosphaturic action of parathyrin and calcitonin (author's transl)]. Oberleithner, H., Lang, F., Greger, R., et al.[2006]

References

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

Parathyroidectomy leads to decreased blood lead levels in patients with refractory secondary hyperparathyroidism. [2016]

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

Decreased blood lead levels after calcitriol treatment in hemodialysis patients with secondary hyperparathyroidism. [2016]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and Pharmacodynamic Characteristics of Subcutaneously Applied PTH-1-37. [2022]

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

Safety of parathyroid hormone for the treatment of osteoporosis. [2021]

5. Austria pubmed.ncbi.nlm.nih.gov

[Additive phosphaturic action of parathyrin and calcitonin (author's transl)]. [2006]